lnu.sePublications
Change search
Refine search result
12 1 - 50 of 76
CiteExportLink to result list
Permanent link
Cite
Citation style
  • apa
  • harvard1
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf
Rows per page
  • 5
  • 10
  • 20
  • 50
  • 100
  • 250
Sort
  • Standard (Relevance)
  • Author A-Ö
  • Author Ö-A
  • Title A-Ö
  • Title Ö-A
  • Publication type A-Ö
  • Publication type Ö-A
  • Issued (Oldest first)
  • Issued (Newest first)
  • Created (Oldest first)
  • Created (Newest first)
  • Last updated (Oldest first)
  • Last updated (Newest first)
  • Disputation date (earliest first)
  • Disputation date (latest first)
  • Standard (Relevance)
  • Author A-Ö
  • Author Ö-A
  • Title A-Ö
  • Title Ö-A
  • Publication type A-Ö
  • Publication type Ö-A
  • Issued (Oldest first)
  • Issued (Newest first)
  • Created (Oldest first)
  • Created (Newest first)
  • Last updated (Oldest first)
  • Last updated (Newest first)
  • Disputation date (earliest first)
  • Disputation date (latest first)
Select
The maximal number of hits you can export is 250. When you want to export more records please use the 'Create feeds' function.
  • 1. Ahrenstedt, Örjan
    et al.
    Knutson, L
    Nilsson, B
    Nilsson Ekdahl, Kristina
    University Hospital, Uppsala.
    Odlind, B
    Hällgren, R
    Enhanced local production of the complement components in the small intestine in Crohn's disease1990In: New England Journal of Medicine, ISSN 0028-4793, E-ISSN 1533-4406, Vol. 322, p. 1345-1349Article in journal (Refereed)
    Abstract [en]

    There is evidence that complement components may be formed locally in inflammatory lesions containing monocytes and macrophages. To investigate the role of complement in Crohn's disease we measured jejunal-fluid concentrations of the complement components C4, C3, and factor B by perfusion of a closed segment of the jejunum in 22 patients with Crohn's disease thought to be limited to the terminal ileum.

    The mean (±SEM) jejunal-fluid C4 concentration was 2.0±0.3 mg per liter, significantly higher than the mean level in 35 healthy controls (0.7±0.1 mg per liter; P<0.001). The mean C3 concentration was 1.0±0.1 mg per liter in the patients and 0.7±0.1 mg per liter in the controls (P<0.05). The factor B levels were similar in the two groups. Calculated rates of intestinal secretion of these components showed differences of the same magnitude. Leakage of protein from plasma was not increased. The jejunal-fluid serum ratios of these complement proteins indicated that their appearance in the lumen of the jejunum was due at least in part to local mucosal synthesis. The increased jejunal secretion of C4, but not C3 or factor B, paralleled the clinical activity of Crohn's disease. Values were normal in first-degree relatives of the patients (n = 13), patients with celiac disease (n = 8), and patients with ulcerative colitis (n = 4).

    We conclude that increased secretion of complement by clinically unaffected jejunal tissue in patients with Crohn's disease reflects the systemic nature of this disorder and may be due to the stimulated synthesis of complement by activated intestinal monocytes and macrophages. 

  • 2. Alston-Smith, J
    et al.
    Boija, P O
    Ware, J
    Nilsson Ekdahl, Kristina
    Department of Clinical Immunology and Transfusion Medicine, University Hospital, Uppsala.
    Endotoxin, epinephrine, glucagon, insulin and calcium ionophore A23187 modulation of pyruvate kinase activity in cultured rat hepatocytes1990In: Acta chirurgica Scandinavica, Vol. 156, no 10, p. 677-681Article in journal (Refereed)
    Abstract [en]

    Altered glucose metabolism is one of the commonly observed sequelae of sepsis and septic shock. The present investigation was undertaken to determine the role of endotoxin (ET) upon hepatocyte glucoregulation, by measuring the activity of pyruvate kinase (PK), a key glycolytic enzyme. Hepatocytes were exposed to endotoxin concentrations known to occur in vivo during sepsis, i.e., from 1 X 10(-14) to 1 X 10(-8) g/ml. The alteration of the enzyme activities after addition of epinephrine, glucagon, insulin and calcium ionophore A23187 with and without ET preincubation were also examined. ET alone decreased the PK activity by 12% at all concentrations tested. The basal inhibition of the enzyme caused by epinephrine (-48%) was partially blocked by ET preincubation above 1 X 10(-10) g/ml. There were no ET-(glucagon, calcium ionophore, insulin) interaction. These in vitro results do not support pyruvate kinase as a site of hepatic enzyme regulation defect in endotoxaemia. 

  • 3. Alston-Smith, J
    et al.
    Ljungqvist, O
    Ware, J
    Nilsson Ekdahl, Kristina
    Department of Clinical Immunology and Transfusion Medicine, University Hospital, Uppsala.
    Regulation of rat hepatocyte fructose 1,6-diphosphatase activity during endotoxemia1991In: Surgical research communications, ISSN 0882-9233, Vol. 11, p. 67-75Article in journal (Refereed)
  • 4. Babiker, Adil A
    et al.
    Magnusson, Peetra U
    Ronquist, Gunnar
    Nilsson, Bo
    Nilsson Ekdahl, Kristina
    Linnaeus University, Faculty of Science and Engineering, School of Natural Sciences.
    Mapping Pro- and Antiangiogenic Factors on the Surface of Prostasomes of Normal and Malignant Cell Origin2010In: The Prostate, ISSN 0270-4137, E-ISSN 1097-0045, Vol. 70, no 8, p. 834-847Article in journal (Refereed)
    Abstract [en]

    BACKGROUND. Angiogenesis is the formation of new blood vessels by capillary sprouting from pre-existing vessels. Tumor growth is angiogenesis-dependent and the formation of new blood vessels is associated with the increased expression of angiogenic factors. Prostasomes are secretory granules produced, stored and released by the glandular epithelial cells of the prostate. We investigated the expression of selected angiogenic and anti-angiogenic factors on the surface of prostasomes of different origins as well as the direct effect of prostasomes on angiogenesis.

    METHODS. VEGF, endothelin-1, endostatin, and thrombospondin-1 were determined on prostasomes from seminal fluid and human prostate cancer cell lines (DU145,PC-3,LNCaP) using different immunochemical techniques. Human dermal microvascular endothelial cells were incubated with seminal and DU145 cell-prostasomes and with radioactive thymidine. The effect of prostasomes on angiogenesis was judged by measuring the uptake of labeled thymidine. The presence of any deleterious effects of prostasomes on the endothelial cells was investigated using thymidine assay and confocal laser microscopy.

    RESULTS. VEGF and endothelin-1 were determined on malignant cell-prostasomes (no difference between cell lines) but not determined on seminal prostasomes. The same applies for the expression of endostatin but with much higher expression on malignant cell-prostasomes with obvious differences between them. Seminal and DU145 cell-prostasomes were found to have anti-angiogenic effect which was more expressed by DU145 cell-prostasomes. No deleterious effect of prostasomes on endothelial function was detected using either thymidine assay or microscopy.

    CONCLUSIONS. Prostasomes contain pro- and anti-angiogenic factors that function to counteract each other unless the impact from one side exceeds the other to bring about dysequilibrium.

  • 5. Babiker, Adil A
    et al.
    Ronquist, Gunnar
    Nilsson, Bo
    Nilsson Ekdahl, Kristina
    Linnaeus University, Faculty of Science and Engineering, School of Natural Sciences.
    Prostasome Involvement in the Development and of Prostate Cancer2010In: Open Prostate Cancer Journal, ISSN 1876-8229, Vol. 3, p. 1-13Article, review/survey (Refereed)
    Abstract [en]

    Prostasomes are extracellularly occurring submicron, membrane-surrounded organelles produced by the epithelial cells of the prostate and present in semen after secretion. Even dedifferentiated prostate cancer cells have preserved their ability to produce and export prostasomes to the extracellular space. The precise physiological role of prostasomes is not known, although some of their properties assign them to important physiological and patho-physiological functions that could be exploited in prostate cancer growth and development. In this review, some new properties of seminal and malignant cell line (DU145, PC-3 and LNCaP) prostasomes will be discussed.There are typical differences in the expressions and activities of prostasomal CD59, ATPase, protein kinases and tissue factor (TF) as well as in the transfer of prostasomal CD59 to CD59-deficient erythrocytes (rabbit and human PNH erythrocytes). CD59, protein kinases and TF exhibit characteristic patterns of overexpression by malignant cell prostasomes. A high ATPase activity is recognized on seminal prostasomes with minimal activity on malignant cell prostasomes resulting in more residual ATP available for phosphorylation reactions. Several proteins are phosphorylated by prostasomal protein kinases, namely, complement component C3, fibrinogen, vitronectin and E-cadherin. Furthermore, TF is identified as the main endogenous phosphorylation substrate on prostasomes. In addition, prothrombotic effects of prostasomes are demonstrated. DU145 and PC-3 cell-derived prostasomes exert a higher clotting effect on whole blood and plasma compared to LNCaP cell-derived and seminal prostasomes.In conclusion, malignant cell prostasomes show an increased ability to interact with the biological system in favor of prostate cancer cell promotion and survival. The roles played by prostasomes in this context may improve the understanding of the mechanisms that help the prostate cancer cells to avoid the complement attack (CD59 transfer and phosphorylation and inactivation of C3), to promote angiogenesis (TF) and to metastasize. It may also provide a better understanding of some of the complications usually seen in some terminal prostate cancer patients like thrombotic events and tendency to develop disseminated intravascular coagulation.

  • 6.
    Barratt-Due, Andreas
    et al.
    Oslo University Hospital, Norway ; University of Oslo, Norway.
    Pischke, Søren Erik
    Oslo University Hospital, Norway ; University of Oslo, Norway.
    Nilsson, Per H.
    Oslo University Hospital, Norway ; University of Oslo, Norway.
    Espevik, Terje
    Norwegian University of Science and Technology, Norway.
    Mollnes, Tom Eirik
    Norwegian University of Science and Technology, Norway ; Norwegian University of Science and Technology, Norway ; Nordland Hospital, Norway ; University of Tromsø, Norway.
    Dual inhibition of complement and Toll-like receptors as a novel approach to treat inflammatory diseases-C3 or C5 emerge together with CD14 as promising targets.2017In: Journal of Leukocyte Biology, ISSN 0741-5400, E-ISSN 1938-3673, Vol. 101, no 1, p. 193-204Article in journal (Refereed)
    Abstract [en]

    The host is protected by pattern recognition systems, including complement and TLRs, which are closely cross-talking. If improperly activated, these systems might induce tissue damage and disease. Inhibition of single downstream proinflammatory cytokines, such as TNF, IL-1β, and IL-6, have failed in clinical sepsis trials, which might not be unexpected, given the substantial amounts of mediators involved in the pathogenesis of this condition. Instead, we have put forward a hypothesis of inhibition at the recognition phase by "dual blockade" of bottleneck molecules of complement and TLRs. By acting upstream and broadly, the dual blockade could be beneficial in conditions with improper or uncontrolled innate immune activation threatening the host. Key bottleneck molecules in these systems that could be targets for inhibition are the central complement molecules C3 and C5 and the important CD14 molecule, which is a coreceptor for several TLRs, including TLR4 and TLR2. This review summarizes current knowledge of inhibition of complement and TLRs alone and in combination, in both sterile and nonsterile inflammatory processes, where activation of these systems is of crucial importance for tissue damage and disease. Thus, dual blockade might provide a general, broad-acting therapeutic regimen against a number of diseases where innate immunity is improperly activated.

  • 7.
    Berg, Aase
    et al.
    Stavanger University Hospital, Norway ; University of Bergen, Norway.
    Otterdal, Kari
    Oslo University Hospital Rikshospitalet, Norway.
    Patel, Sam
    Central Hospital of Maputo, Mozambique.
    Gonca, Miguel
    Central Hospital of Maputo, Mozambique.
    David, Catarina
    Central Hospital of Maputo, Mozambique.
    Dalen, Ingvild
    Stavanger University Hospital, Norway.
    Nymo, Stig
    Oslo University Hospital Rikshospitalet, Norway.
    Nilsson, Margareta
    Oslo University Hospital Rikshospitalet, Norway.
    Nordling, Sofia
    Uppsala University.
    Magnusson, Peetra U
    Uppsala University.
    Ueland, Thor
    Oslo University Hospital Rikshospitalet, Norway.
    Prato, Mauro
    University of Torino, Italy.
    Giribaldi, Giuliana
    University of Torino, Italy.
    Mollnes, Tom Eirik
    Oslo University Hospital Rikshospitalet, Norway.
    Aukrust, Pål
    Oslo University Hospital Rikshospitalet, Norway.
    Langeland, Nina
    University of Bergen, Norway.
    Nilsson, Per H.
    Oslo University Hospital Rikshospitalet, Norway.
    Complement Activation Correlates With Disease Severity and Contributes to Cytokine Responses in Plasmodium falciparum Malaria.2015In: Journal of Infectious Diseases, ISSN 0022-1899, E-ISSN 1537-6613, Vol. 212, no 11, p. 1835-1840Article in journal (Refereed)
    Abstract [en]

    The impact of complement activation and its possible relation to cytokine responses during malaria pathology was investigated in plasma samples from patients with confirmed Plasmodium falciparum malaria and in human whole-blood specimens stimulated with malaria-relevant agents ex vivo. Complement was significantly activated in the malaria cohort, compared with healthy controls, and was positively correlated with disease severity and with certain cytokines, in particular interleukin 8 (IL-8)/CXCL8. This was confirmed in ex vivo-stimulated blood specimens, in which complement inhibition significantly reduced IL-8/CXCL8 release. P. falciparum malaria is associated with systemic complement activation and complement-dependent release of inflammatory cytokines, of which IL-8/CXCL8 is particularly prominent.

  • 8.
    Bergseth, Grethe
    et al.
    Nordland Hospital, Bodø, Norway.
    Nilsson, Per H.
    University of Oslo, Rikshospitalet, Norway.
    Thomas, Anub Mathew
    Radboud University Medical Center, The Netherlands.
    Gustavsen, Alice
    University of Oslo, Rikshospitalet, Norway.
    Volokhina, Elena B
    Radboud University Medical Center, The Netherlands.
    van den Heuvel, Lambertus P
    Radboud University Medical Center, The Netherlands.
    Barratt-Due, Andreas
    University of Oslo, Rikshospitalet, Norway.
    Mollnes, Tom E
    University of Oslo, Rikshospitalet, Norway;Nordland Hospital, Norway;University of Tromsø, Norway.
    Neoepitope based assays to detect C5a – Pitfalls and interpretations2017In: Molecular Immunology, ISSN 0161-5890, E-ISSN 1872-9142, Vol. 89, no SI: EMCHD2017, p. 201-201Article in journal (Refereed)
  • 9.
    Bexborn, Fredrik
    et al.
    University of Kalmar, School of Pure and Applied Natural Sciences.
    Engberg, Anna E.
    University of Kalmar, School of Pure and Applied Natural Sciences.
    Sandholm, Kerstin
    University of Kalmar, School of Pure and Applied Natural Sciences.
    Mollnes, Tom Eirik
    Hong, Jaan
    Nilsson Ekdahl, Kristina
    University of Kalmar, School of Pure and Applied Natural Sciences.
    Hirudin versus heparin for use in whole blood in vitro biocompatibility models2009In: Journal of Biomedical Materials Research. Part A, ISSN 1549-3296, E-ISSN 1552-4965, Vol. 89A, no 4, p. 951-959Article in journal (Refereed)
    Abstract [en]

    Background: Heparin has traditionally been a widely used anticoagulant in blood research, but has been shown to be inappropriate for work with the complement system because of its complement-interacting properties. In this work, we have compared the effects of heparin with those of the specific thrombin inhibitor hirudin on complement and blood cells in vitro.

    Methods: Whole blood collected in the presence of hirudin (50 µg/mL) or heparin (1 IU/mL) was incubated in the slide chamber model. The plasma was analyzed for complement activation markers C3a and sC5b-9, and the polyvinylchloride test slides were stained for adhering cells. The integrity of the complement system was tested by incubating serum and hirudin-treated plasma in the presence of various activating agents.

    Results: In contrast to heparin, the addition of hirudin generally preserved the complement reactivity, and complement activation in hirudin plasma closely resembled that in normal serum. Importantly, immunochemical staining of surface-bound cells demonstrated the inducible expression of tissue factor on bound monocytes from hirudin-treated blood, an effect that was completely abolished in heparin-treated blood.

    Conclusion: Our results indicate that hirudin as an anticoagulant produces more physiological conditions than heparin, making hirudin well-suited for in vitro studies, especially those addressing the regulation of cellular processes.

  • 10.
    Blomberg, Carolina
    University of Kalmar, School of Pure and Applied Natural Sciences.
    Intrathecal and Systemic Complement Activation Studies of Multiple Sclerosis and Guillan-Barré Syndrome2009Independent thesis Advanced level (degree of Master (One Year)), 20 credits / 30 HE creditsStudent thesis
    Abstract [en]

    Both Multiple Sclerosis (MS) and Guillan-Barré syndrome (GBS) are neurological inflammatory demyelinating autoimmune diseases, with a probable antibody contribution. Complement proteins in both MS and GBS does play a role in inflammation and demyelination at pathogenesis, according to earlier scientific evidence. The aim of this examination project work was to investigate systemic and intrathecal complement activation in MS and GBS, to gain further knowledge that might be useful for development of future therapeutics targeting immune responses during those diseases. An additional aim was to develop a new ELISA method for detection of complement iC3.

    By using sandwich ELISA, complement proteins C1q, C4, C3, fH and C3a were measured in plasma and cerebrospinal fluid (CSF) from persons within 4 different diagnostic groups; MS, other neurological diseases (OND), GBS and controls (C). An ELISA method to detect iC3 (hydrolysed C3) was also developed, including usage of SDS-PAGE. Results based on raw data and statistical analysis show significantly elevated levels of C3a (C3a/C3) in MS and decreased C3 in plasma. In CSF low levels of C4 and C3a/C3 in MS were detected, though correlation of C3a and C1q was positive. GBS reveal high levels of all complement proteins analysed in CSF except for C3, and a positive correlation of C3a and C1q as well as C3a and fH was found.

    These results indicate that MS patients have systemic complement activation; however the activation pathway is not determined. Complement activation in MS may also occur intrathecally, with correlation analysis indicating a possible activation via the classical pathway. MS patients suffering from a more acute relapsing-remitting (RR) MS have a more prominent systemic complement activation compared to MS patients responding to beta-interferon treatment. Systemic increased C3a/C3 ratio may be a possible biomarker to distinguish more acute RR MS in an earlier step of MS pathogenesis and should be further investigated. GBS patients have an intrathecal complement activation that seems to occur via the classical pathway.

  • 11. Boij, Roland
    et al.
    Svensson, Judit
    Nilsson Ekdahl, Kristina
    Linnaeus University, Faculty of Science and Engineering, School of Natural Sciences.
    Sandholm, Kerstin
    Linnaeus University, Faculty of Science and Engineering, School of Natural Sciences.
    Lindahl, Tomas
    Palonek, Elzbieta
    Garle, Mats
    Berg, Mats
    Ernerudh, Jan
    Jenmalm, Mats
    Matthiesen, Leif
    Biomarkers of coagulation, inflammation and angiogenesis are independently associated with preeclampsia2012In: American Journal of Reproductive Immunology and Microbiology, ISSN 8755-8920, Vol. 68, no 3, p. 258-270Article in journal (Refereed)
    Abstract [en]

    Problem Although preeclampsia has been associated with inflammation, coagulation, and angiogenesis, their correlation and relative contribution are unknown. Method of Study About 114 women with preeclampsia, 31 with early onset (EOP) and 83 with late onset preeclampsia (LOP), and 100 normal pregnant controls were included. A broad panel of 32 biomarkers reflecting coagulation, inflammation, and angiogenesis was analyzed. Results Preeclampsia was associated with decreased antithrombin, IL-4 and placental growth factor levels and with increased C3a, pentraxin-3, and sFlt-1 levels, with more marked differences in the EOP group. The Th1-associated chemokines CXCL10 and CXCL11 were significantly higher in the preeclampsia and EOP group than in controls, respectively. No correlations between the biomarkers were found in preeclampsia. Multivariate logistic regression tests confirmed the results. Conclusions Cytokines, chemokines and complement activation seem to be part of a Th1-like inflammatory reaction in preeclampsia, most pronounced in EOP, where chemokines may be more useful than cytokines as biomarkers. Biomarkers were not correlated suggesting partly independent or in time separated mechanisms.

  • 12. Boija, P O
    et al.
    Nilsson Ekdahl, Kristina
    Department of Medical and Physiological Chemistry, University of Uppsala.
    Nylander, G
    Ware, J
    Hemorrhagic hypotension and hepatic cell pyruvate kinase and fructose-1,6-diphosphatase activity in vivo1987In: Surgical research communications, Vol. 2, p. 119-124Article in journal (Refereed)
  • 13. Bäck, Jennie
    et al.
    Sanchez, Javier
    Elgue, Graciela
    Nilsson Ekdahl, Kristina
    Linnaeus University, Faculty of Science and Engineering, School of Natural Sciences.
    Nilsson, Bo
    Activated platelets induce FXII-mediated contact activation2010In: Biochemical and Biophysical Research Communications - BBRC, ISSN 0006-291X, E-ISSN 1090-2104, Vol. 391, no 1, p. 11-17Article in journal (Refereed)
    Abstract [en]

    Earlier studies have shown that isolated platelets in buffer systems can promote activation of FXII or amplify contact activation. in the presence of it negatively charge Substance or material Still proof is lacking that FXII is activated by platelets in a more physiological environment In this study we investigate if activated platelets can induce FXII-mediated contact activation and whether this activation affects clot formation in human blood.

    Human platelets were activated with a thrombin receptor-activating peptide, SFLLRN-amide, in platelet-rich plasma or in whole blood. FXIIa and FXIa in complex with preferentially antithrombin (AT) and to some extent C1-inhibitor (C1INH) were generated in response to TRAP stimulation. This contact activation was independent of surface-mediated contact activation, tissue factor pathway or thiombin. In clotting whole blood FXIIa-AT and FXIa-AT complexes were specifically formed. demonstrating that AT is a potent inhibitor of FXIIa and FXIa generated by platelet activation Contact activation proteins were analyzed by flow cytometry and FXII, FXI, high-molecular weight kininogen, and prekallikrein were detected oil activated platelets Using chromogenic assays, enzymatic activity of platelet-associated FXIIa, FXIa, and kallikrein were demonstrated Inhibition of FXIIa in non-anticoagulated blood also prolonged the clotting time.

    We conclude that platelet activation triggers FXII-mediated contact activation oil the Surface and in the vicinity of activated platelets This leads specifically to generation of FXIIa-AT and FXIa-AT complexes, and contributes to clot formation Activated platelets may thereby constitute an intravascular locus for contact activation, which may explain the recently reported importance of FXII in thrombus formation (C) 2009 Published by Elsevier Inc.

  • 14.
    Christensen, Kjeld
    et al.
    Örebro University Hospital.
    Kozarcanin, Huda
    Uppsala University.
    Nilsson Ekdahl, Kristina
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences. Uppsala University.
    Nilsson, Bo
    Uppsala University.
    Evidence of contact activation in patients suffering from ST-elevation myocardial infarction2016In: Thrombosis Research, ISSN 0049-3848, E-ISSN 1879-2472, Vol. 141, p. 158-162Article in journal (Refereed)
    Abstract [en]

    Introduction: Factor (F) XIIa is an attractive target for anticoagulation in arterial thrombosis. The aim of this study is to investigate the degree of involvement of the contact system in cardiac infarctions. Methods and patients: 165 patients suffering from ST-elevation myocardial infarction (STEMI) and 100 healthy controls were included in the study. Samples were drawn at admission before percutaneous intervention (PCI), 1-3 days post-percutaneous intervention (PCI) and, in one-third of the patients, 3 months after PCI. In order to investigate the degree of Factor XII (FXII) activation, changes in FXIIa/AT and FXIIa/C1INH complex levels were quantified by ELISA. Results: FXIIa/AT levels at admission (0.89 +/- 0.50; p < 0.01) were significantly higher than those in normal individuals (0.39 +/- 0.28), but the levels after 1-3 days (0.33 +/- 0.33; p < 0.05) were essentially normalized. In contrast, the FXII/C1INH levels at admission (1.40 +/- 0.72; p < 0.001) and after 1-3 days (0.83 +/- 0.59; p < 0.001) were both significantly higher than those in normal individuals (0.40 +/- 0.30). FXIIa/AT and FXIIa/C1INH complexes at admission (p < 0.001; p < 0.001) and after 1-3 days (p < 0.02; p < 0.001) were significantly different from those at 3 months. No significant differences were observed when the data were stratified for patency (open/closed culprit lesions). Conclusion: Both FXIIa/AT and FXIIa/C1INH complexes were significantly increased and reflected the activation of FXII in STEMI patients at admission. In particular, FXIIa/AT complex elevations support the hypothesis that clot propagation-mediated FXII activation had occurred, and this activation may be a target for anticoagulation in patients with cardiac infarction. Based on previous studies, the FXIIa/C1INH complex levels were primarily interpreted to reflex endothelial cell activation. (C) 2016 Published by Elsevier Ltd.

  • 15. Demirel, Isak
    et al.
    Vumma, Ravi
    Mohlin, Camilla
    Linnaeus University, Faculty of Science and Engineering, School of Natural Sciences.
    Svensson, Lovisa
    Linnaeus University, Faculty of Science and Engineering, School of Natural Sciences.
    Säve, Susanne
    Linnaeus University, Faculty of Science and Engineering, School of Natural Sciences.
    Persson, Katarina
    Linnaeus University, Faculty of Science and Engineering, School of Natural Sciences.
    Nitric Oxide Activates IL-6 Production and Expression in Human Renal Epithelial Cells2012In: American Journal of Nephrology, ISSN 0250-8095, E-ISSN 1421-9670, Vol. 36, no 6, p. 524-530Article in journal (Refereed)
    Abstract [en]

    Background/Aims: Increased nitric oxide (NO) production or inducible form of NO synthase activity have been documented in patients suffering from urinary tract infection (UTI), but the role of NO in this infection is unclear. We investigated whether NO can affect the host response in human renal epithelial cells by modulating IL-6 production and mRNA expression. Methods: The human renal epithelial cell line A498 was infected with a uropathogenic Escherichia coli (UPEC) strain and/or the NO donor DETA/NO. The IL-6 production and mRNA expression were evaluated by ELISA and real-time RT-PCR. IL-6 mRNA stability was evaluated by analyzing mRNA degradation by real-time RT-PCR. Results: DETA/NO caused a significant (p < 0.05) increase in IL-6 production. Inhibitors of p38 MAPK and ERK1/2 signaling, but not JNK, were shown to significantly suppress DETA/NO-induced IL-6 production. UPEC-induced IL-6 production was further increased (by 73 +/- 23%, p < 0.05) in the presence of DETA/NO. The IL-6 mRNA expression increased 2.1 +/- 0.17-fold in response to DETA/NO, while the UPEC-evoked increase was pronounced (20 +/- 4.5-fold). A synergistic effect of DETA/NO on UPEC-induced IL-6 expression was found (33 +/- 7.2-fold increase). The IL-6 mRNA stability studies showed that DETA/NO partially attenuated UPEC-induced degradation of IL-6 mRNA. Conclusions: NO was found to stimulate IL-6 in renal epithelial cells through p38 MAPK and ERK1/2 signaling pathways and also to increase IL-6 mRNA stability in UPEC-infected cells. This study proposes a new role for NO in the host response during UTI by modulating the transcription and production of the cytokine IL-6. Copyright (C) 2012 S. Karger AG, Basel

  • 16.
    Engberg, Anna E.
    Linnaeus University, Faculty of Science and Engineering, School of Natural Sciences.
    Biomaterials and Hemocompatibility2010Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Biomaterials are commonly used in the medical clinic today; however, artificial materials can activate the cascade systems in the blood (complement-, coagulation-, contact- and fibrinolytic systems) as well as the platelets to various degrees. When an artificial surface comes in contact with blood, plasma proteins will be adsorbed to the surface within seconds. The composition of the layer of proteins differs between materials and is crucial for the hemocompatibility of the material.

    This thesis includes five projects.

    In Paper I the anticoagulants heparin and the thrombin inhibitor hirudin were evaluated in a whole blood model. Hirudin was found to be superior to low dose heparin since it did not affect the activation of the complement system nor the leukocytes. The most interesting observation was that expression of TF was seen on surface-attached monocytes in hirudin- treated blood but not heparin blood.

    In Paper II peptides from the streptococcal M-protein, which has affinity for the human complement inhibitor C4BP, were attached to a polymeric surface. When being exposed to blood the endogenous complement regulator was enriched at the surface of the material, via the M-peptides. With this new approach we created a self-regulatory surface, showing significant lowered material-induced complement activation.

    In Paper III apyrase, an enzyme which hydrolyzes nucleoside ATP and ADP, was immobilized on a polymer surface. Lower platelet activation and platelet-induced coagulation activation was seen for the apyrase-coated surface compared to control surfaces after exposure to whole human blood, due to the enzymes capability to degrade ADP released from activated platelets.

    In Paper IV and V we synthesized an array of polymeric materials which were characterized regarding physical-chemical properties, adsorption of plasma proteins, and hemocompatibility. The polymers showed widely heterogeneous protein adsorption. Furthermore, when the polymers were exposed to whole blood, two of the materials showed superior hemocompatibility (monitored as complement- and coagulation activation), compared to the reference poly(vinyl chloride).

  • 17.
    Engberg, Anna E.
    et al.
    University of Kalmar, School of Pure and Applied Natural Sciences.
    Rosengren-Holmberg, Jenny P
    University of Kalmar, School of Pure and Applied Natural Sciences.
    Nilsson, Per H.
    University of Kalmar, School of Pure and Applied Natural Sciences.
    Bäck,
    Department of Oncology, Radiology and Clinical Immunology, Section of Clinical Immunology, Rudbeck Laboratory C5, Uppsala University Hospital, SE-751 85 Uppsala, Sweden.
    Mollnes, Tom Eirik
    Institute of Immunology, Rikshospitalet University Hospital, Oslo, Norway,Research Laboratory, Nordland Hospital, Bodø, and University of Tromsø, Norway.
    Nicholls, Ian A.
    University of Kalmar, School of Pure and Applied Natural Sciences.
    Nilsson, Bo
    Department of Oncology, Radiology and Clinical Immunology, Section of Clinical Immunology, Rudbeck Laboratory C5, Uppsala University Hospital, SE-751 85 Uppsala, Sweden.
    Nilsson Ekdahl, Kristina
    University of Kalmar, School of Pure and Applied Natural Sciences.
    EVALUATION OF THE HEMOCOMPATIBILITY OF NOVEL POLYMERIC MATERIALSManuscript (preprint) (Other academic)
    Abstract [en]

    When a biomaterial surface comes in contact with blood an immediate adsorption of plasma proteins to the surface will occur, and the cascade systems in the blood, such as the complement, coagulation and contact system, will be activated to various degrees. The intensity of this reaction will determine the hemocompatibility of the materials. Here we present an evaluation of the link between the composition, the physico-chemical properties and the protein adsorption properties of six newly synthesized polymers (P1-P6) and the hemocompatibility.The hemocompatibility of the polymeric surfaces was evaluated in human blood plasma and whole blood. Commercially available polyvinylchloride (PVC) was used as reference material. The hemocompatibility of the polymeric surfaces was evaluated with regard to complement activation (C3a and sC5-9 generation) and coagulation activation (platelet loss and TAT-formation) and cytokine productions (27 analytes in multiplex assay) after contact with whole blood. Contact activation was quantified by analyses of FXIIa-C1INH, FXIa-C1INH, and kallikrein-C1INH complexes.Polymers P2 (p<0.05 for C3a), P3, P5 and P6 showed less complement activation, and polymers P1 and P4 (p<0.05 for platelet loss), as well as P5 and P6 showed less coagulation activation compared with reference PVC. Polymers P1-P3 induced activation of the contact system, P3 being the most potent. Secretion of 17 cytokines including chemokines and growth factors were differentially influenced by the polymers, P1 and P3 being significantly (p<0.05) more compatible for five of the analytes.Collectively these data demonstrate that the composition of the polymers clearly leads to different biological properties as a consequence of distinctive physico-chemical properties and protein adsorption patterns.1

  • 18.
    Engberg, Anna
    et al.
    University of Kalmar, School of Pure and Applied Natural Sciences.
    Rosengren-Holmberg, Jenny
    University of Kalmar, School of Pure and Applied Natural Sciences.
    Chen, Hui
    Department of Pathology, University of Pennsylvania, 401 Stellar Chance, Philadelphia, PA 19104, USA.
    Lambris, John
    Department of Pathology, University of Pennsylvania, 401 Stellar Chance, Philadelphia, PA 19104, USA.
    Nicholls, Ian
    University of Kalmar, School of Pure and Applied Natural Sciences.
    N. Ekdahl, Kristina
    University of Kalmar, School of Pure and Applied Natural Sciences.
    BLOOD PROTEIN-POLYMER ADSORPTION FINGERPRINTING:IMPLICATIONS FOR UNDERSTANDING HEMOCOMPATIBILITYAND FOR BIOMATERIAL DESIGNManuscript (preprint) (Other academic)
    Abstract [en]

    Within seconds after an artificial material has been implanted into the blood thesurface will be covered by adsorbed plasma proteins. The composition of theprotein layer is determined by the physical-chemical properties of the surface. Asthe layer itself will become the new interface between the material and blood, itis of major importance for the hemocompatibility. In this project we have studiedthe adsorption of proteins to a model material (polystyrene, PS) with the peptidemass fingerprint technique (PMF) analyzed on a Matrix Assisted LaserDesorption/Ionization Time-of-Flight (MALDI-TOF). To further be able to studythe adsorption of plasma proteins to polymer surfaces, we have synthesized 33new polymer compositions with variable surface properties. Six of thosepolymers were selected and their protein binding ability was determined as wellas quantification of adsorption of 20 plasma proteins to the surface of thepolymers. Our results showed that fourteen high abundant plasma proteins werepositively identified on the PS-surface by MALDI-TOF. Further, the resultsshowed that the synthesized polymers had very distinctive adsorption patterns,with enrichment of different proteins after incubation in plasma and serum. Oneof the polymers was shown to adsorb large amounts of the complementactivating recognition protein C1q, which makes this polymer to a potentialactivating surface. Two of the polymers showed a clear enrichment of thecomplement regulating protein vitronectin as well as two apolipoproteins (AI andAIV) to the surface of the polymers, while some of the polymers bound proteinsapproximately in correlation to the concentration found in plasma.

  • 19.
    Fernández Sjödin, Susana
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    I fotspåren av forskarnas jakt efter lösningen på gåtan: sambandet mellan narkolepsi och influensavaccinet Pandemrix2017Independent thesis Basic level (degree of Bachelor), 10 credits / 15 HE creditsStudent thesis
  • 20.
    Fretland, Asmund Avdem
    et al.
    The Intervention Centre, Oslo University Hospital, Norway.
    Sokolov, Andrey
    Oslo University Hospital, Norway.
    Postriganova, Nadya
    Intervention Centre, Oslo University Hospital, Norway.
    Kazaryan, Airazat M
    Intervention Centre, Oslo University Hospital, Norway.
    Pischke, Soren E
    Intervention Centre, Oslo University Hospital, Norway.
    Nilsson, Per H.
    Oslo University Hospital, Norway.
    Rognes, Ingrid Nygren
    Oslo University Hospital, Norway.
    Bjornbeth, Bjorn Atle
    Oslo University Hospital, Norway.
    Fagerland, Morten Wang
    Oslo University Hospital, Norway.
    Mollnes, Tom Eirik
    Oslo University Hospital, Norway.
    Edwin, Bjorn
    Intervention Centre, Oslo University Hospital, Norway.
    Inflammatory Response After Laparoscopic Versus Open Resection of Colorectal Liver Metastases: Data From the Oslo-CoMet Trial.2015In: Medicine (Baltimore, Md.), ISSN 0025-7974, E-ISSN 1536-5964, Vol. 94, no 42, p. 1-7, article id e1786Article in journal (Refereed)
    Abstract [en]

    Laparoscopic and open liver resection have not been compared in randomized trials. The aim of the current study was to compare the inflammatory response after laparoscopic and open resection of colorectal liver metastases (CLM) in a randomized controlled trial.This was a predefined exploratory substudy within the Oslo CoMet-study. Forty-five patients with CLM were randomized to laparoscopic (n = 23) or open (n = 22) resection. Ethylenediaminetetraacetic acid-plasma samples were collected preoperatively and at defined time points during and after surgery and snap frozen at -80 C. A total of 25 markers were examined using luminex and enzyme-linked immunosorbent assay techniques: high-mobility box group 1(HMGB-1), cell-free DNA (cfDNA), cytokines, and terminal C5b-9 complement complex complement activation.Eight inflammatory markers increased significantly from baseline: HMGB-1, cfDNA, interleukin (IL)-6, C-reactive protein, macrophage inflammatory protein -1β, monocyte chemotactic protein -1, IL-10, and terminal C5b-9 complement complex. Peak levels were reached at the end of or shortly after surgery. Five markers, HMGB-1, cfDNA, IL-6, C-reactive protein, and macrophage inflammatory protein -1β, showed significantly higher levels in the open surgery group compared with the laparoscopic surgery group.Laparoscopic resection of CLM reduced the inflammatory response compared with open resection. The lower level of HMGB-1 is interesting because of the known association with oncogenesis.

  • 21.
    Gustafson, Elisabet
    et al.
    Univ Uppsala Hosp..
    Asif, Sana
    Uppsala University.
    Kozarcanin, Huda
    Uppsala University.
    Elgue, Graciela
    Uppsala University.
    Meurling, Staffan
    Univ Uppsala Hosp..
    Nilsson Ekdahl, Kristina
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Nilsson, Bo
    Uppsala University.
    Control of IBMIR Induced by Fresh and Cryopreserved Hepatocytes by Low Molecular Weight Dextran Sulfate Versus Heparin2017In: Cell Transplantation, ISSN 0963-6897, E-ISSN 1555-3892, Vol. 26, no 1, p. 71-81Article in journal (Refereed)
    Abstract [en]

    Rapid destruction of hepatocytes after hepatocyte transplantation has hampered the application of this procedure clinically. The instant blood-mediated inflammatory reaction (IBMIR) is a plausible underlying cause for this cell loss. The present study was designed to evaluate the capacity of low molecular weight dextran sulfate (LMW-DS) to control these initial reactions from the innate immune system. Fresh and cryopreserved hepatocytes were tested in an in vitro whole-blood model using ABO-compatible blood. The ability to elicit IBMIR and the capacity of LMW-DS (100 mu g/ml) to attenuate the degree of activation of the cascade systems were monitored. The effect was also compared to conventional anticoagulant therapy using unfractionated heparin (1 IU/ml). Both fresh and freeze thawed hepatocytes elicited IBMIR to the same extent. LMW-DS reduced the platelet loss and maintained the cell counts at the same degree as unfractionated heparin, but controlled the coagulation and complement systems significantly more efficiently than heparin. LMW-DS also attenuated the IBMIR elicited by freeze thawed cells. Therefore, LMW-DS inhibits the cascade systems and maintains the cell counts in blood triggered by both fresh and cryopreserved hepatocytes in direct contact with ABO-matched blood. LMW-DS at a previously used and clinically applicable concentration (100 mu g/ml) inhibits IBMIR in vitro and is therefore a potential IBMIR inhibitor in hepatocyte transplantation.

  • 22.
    Hamad, Osama
    et al.
    Uppsala University.
    Bäck, Jennie
    Uppsala University.
    Nilsson, Per H.
    Linnaeus University, Faculty of Science and Engineering, School of Natural Sciences.
    Nilsson, Bo
    Uppsala University.
    Nilsson Ekdahl, Kristina
    Uppsala University.
    Platelets, Complement, and Contact Activation: Partners in inflammation and thrombosis2012In: Current Topics in Innate Immunity II / [ed] John D. Lambris &George Hajishengallis, Springer, 2012, Vol. 946, no Current Topics in Innate Immunity II. J. D. Lambris, G. Hajishengallis (eds.), p. 185-205Conference paper (Refereed)
    Abstract [en]

    Platelet activation during thrombotic events is closely associated with complement and contact system activation, which in turn leads to inflammation . Here we review the interactions between activated platelets and the complement and contact activation systems in clotting blood. Chondroitin sulfate A (CS-A), released from alpha granules during platelet activation, is a potent mediator of crosstalk between platelets and the complement system. CS-A activates complement in the fluid phase, generating anaphylatoxins that mediate leukocyte activation. No complement activation seems to occur on the activated platelet surface, but C3 in the form of C3(H2O) is bound to the surfaces of activated platelets . This finding is consistent with the strong expression of membrane-bound complement regulators present at the platelet surface. CS-A exposed on the activated platelets is to a certain amount responsible for recruiting soluble regulators to the surface. Platelet-bound C3(H2O) acts as a ligand for leukocyte CR1 (CD35), potentially enabling platelet–leukocyte interactions. In addition, platelet activation leads to the activation of contact system enzymes, which are specifically inhibited by antithrombin, rather than by C1INH, as is the case when contact activation is induced by material surfaces. Thus, in addition to their traditional role as initiators of secondary hemostasis, platelets also act as mediators and regulators of inflammation in thrombotic events.

  • 23.
    Harboe, M.
    et al.
    Oslo University Hospital Rikshospitalet, Norway.
    Johnson, C.
    Oslo University Hospital Rikshospitalet, Norway.
    Nymo, S.
    Nordland Hospital, Norway.
    Ekholt, K.
    Oslo University Hospital Rikshospitalet, Norway.
    Schjalm, C.
    Oslo University Hospital Rikshospitalet, Norway.
    Lindstad, J. K.
    Oslo University Hospital Rikshospitalet, Norway.
    Pharo, A.
    Oslo University Hospital Rikshospitalet, Norway.
    Hellerud, B. C.
    Oslo University Hospital Rikshospitalet, Norway.
    Nilsson Ekdahl, Kristina
    Uppsala University.
    Mollnes, T. E.
    Oslo University Hospital Rikshospitalet, Norway ; Nordland Hospital, Norway.
    Nilsson, Per H.
    Oslo University Hospital Rikshospitalet, Norway.
    Molecular modelling showed optimal fit between TSR5 in trimeric properdin and C345C in the C3b moiety for stabilization of the alternative convertase, whereas binding to molecular patterns in myeloperoxidase, endothelial cells and Neisseria meningitides was indirectly mediated by initial C3 activation2016In: Immunobiology, ISSN 0171-2985, E-ISSN 1878-3279, Vol. 221, no 10, p. 1205-1205Article in journal (Refereed)
  • 24.
    Harboe, M.
    et al.
    University of Oslo, Rikshospitalet, Norway ; University of Oslo, Norway.
    Nilsson, Per H.
    University of Oslo, Rikshospitalet, Norway ; University of Oslo, Norway.
    Johnson, C.
    University of Oslo, Rikshospitalet, Norway ; University of Oslo, Norway.
    Lindstad, J. K.
    University of Oslo, Rikshospitalet, Norway ; University of Oslo, Norway.
    Pharo, A.
    University of Oslo, Rikshospitalet, Norway ; University of Oslo, Norway.
    Hellerud, B. C.
    University of Oslo, Rikshospitalet, Norway ; University of Oslo, Norway.
    Nymo, S.
    University of Oslo, Rikshospitalet, Norway ; University of Oslo, Norway ; University of Tromsö, Norway.
    Mollnes, T. E.
    University of Oslo, Rikshospitalet, Norway ; University of Oslo, Norway ; University of Tromsö, Norway.
    Binding of properdin to myeloperoxidase and Neisseria meningitidis is C3-dependent2015In: Molecular Immunology, ISSN 0161-5890, E-ISSN 1872-9142, Vol. 67, no 1, Special Issue, p. 142-142, article id 067Article in journal (Refereed)
  • 25.
    Huang, Shan
    et al.
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Sandholm, Kerstin
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Jonsson, Nina
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences. Uppsala University.
    Nilsson, Anders
    Gambro Lundia AB.
    Wieslander, Anders
    Gambro Lundia AB.
    Grundström, Gunilla
    Gambro Lundia AB.
    Hancock, Viktoria
    Gambro Lundia AB.
    Nilsson Ekdahl, Kristina
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences. Uppsala University.
    Low concentrations of citrate reduce complement and granulocyte activation in vitro in human blood2015In: Clinical Kidney Journal, ISSN 2048-8505, E-ISSN 2048-8513, Vol. 8, no 1, p. 31-37Article in journal (Refereed)
    Abstract [en]

    BACKGROUND:The use of acetate in haemodialysis fluids may induce negative effects in patients including nausea and increased inflammation. Therefore, haemodialysis fluids where acetate is substituted with citrate have recently been developed. In this study, we investigated the biocompatibility of citrate employing concentrations used in haemodialysis.

    METHODS:The effects of citrate and acetate were investigated in human whole blood in vitro under conditions promoting biomaterial-induced activation. Complement activation was measured as generation of C3a, C5a and the sC5b-9 complex, and granulocyte activation as up-regulation of CD11b expression. For the experimental set-up, a mathematical model was created to calculate the concentrations of acetate and citrate attained during haemodialysis.

    RESULTS:Citrate reduced granulocyte activation and did not induce higher complement activation compared with acetate at concentrations attained during haemodialysis. Investigating different citrate concentrations clearly showed that citrate is a potent complement inhibitor already at low concentrations, i.e. 0.25 mM, which is comparable with concentrations detected in the blood of patients during dialysis with citrate-containing fluids. Increased citrate concentration up to 6 mM further reduced the activation of C3a, C5a and sC5b-9, as well as the expression of CD11b.

    CONCLUSIONS:Our results suggest that citrate is a promising substitute for acetate for a more biocompatible dialysis, most likely resulting in less adverse effects for the patients.

  • 26.
    Johansson, Emilia
    et al.
    Linnaeus University, Faculty of Health and Life Sciences, Department of Health and Caring Sciences.
    Larsson, Amanda
    Linnaeus University, Faculty of Health and Life Sciences, Department of Health and Caring Sciences.
    När det ofarliga blir farligt: En enkätstudie om hur frekvent matöverkänslighet är bland människor i åldern 18-28 år i Sverige2013Independent thesis Basic level (degree of Bachelor), 10 credits / 15 HE creditsStudent thesis
    Abstract [sv]

    Bakgrund: Att definiera matöverkänslighet är ännu idag inte fastställt, det råder delade meningar om denna definition. Författarna har valt att inrikta sig på matöverkänslighet som definieras matallergi och matintolerans. Flera av matallergierna kan utlösa en allergisk chock, denna typ av chock som även kallas anafylaktisk chock kan vara livshotande om inte behandling sätts in direkt. Idag lider var tredje person i Sverige av någon typ av allergi, vanligt förekommande matöverkänsligheter är komjölksallergi, laktosintolerans, äggallergi och nötallergi.

    Syfte: Syftet är att undersöka hur många människor i åldern 18-28 år som lider utav matöverkänslighet och om allergimedicin bärs med dagligen.

    Metod: En empirisk enkätstudie låg till grund för studiens resultat. Författarna valde att göra en kvantitativ studie för att kunna samla in data systematiskt och sedan sammanfatta dessa i statistisk form. Studien var ute efter ett större antal deltagare utspridda på olika platser så därför passade kvantitativ metod in med en enkätstudie. Det blev en prospektiv tvärsnittsstudie då studien undersöker hur något såg ut vid ett specifikt tillfälle.

    Resultat: Studiens resultat visar att drygt en tredjedel utav deltagarna lider utav någon form utav matöverkänslighet, allergi eller intolerans. Ytterligare 20 % har någon gång reagerat på ett livsmedel, men använder idag ingen medicin mot sina besvär. De vanligaste livsmedlen att reagera emot är mjölk- laktos, frukt, nötter och vete.

    Slutsatser: Knappt hälften av de personerna som deltagit i denna studie har någon gång reagerat på ett livsmedel. Sedan har drygt 35 % utav deltagarna uppgett att de använder någon form utav allergimedicin mot livsmedel. Det innebär att människor i västvärlden är mer matöverkänsliga nu än någonsin och trenden fortsätter att eskalera. Renlighet och matvanor är troligen orsaker till detta växande hälsoproblem. 

  • 27.
    Kozarcanin, H.
    et al.
    Uppsala University.
    Lood, C.
    Skåne University Hospital ; Lund University.
    Munthe-Fog, L.
    University of Copenhagen, Denmark.
    Sandholm, Kerstin
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Hamad, O. A.
    Uppsala University.
    Bengtsson, A. A.
    Skåne University Hospital ; Lund University.
    Skjoedt, M. -O
    University of Copenhagen, Denmark.
    Huber-Lang, M.
    University Hospital of Ulm, Germany.
    Garred, P.
    University of Copenhagen, Denmark.
    Nilsson Ekdahl, Kristina
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences. Uppsala University.
    Nilsson, Bo
    Uppsala University.
    The lectin complement pathway serine proteases (MASPs) represent a possible crossroad between the coagulation and complement systems in thromboinflammation2016In: Journal of Thrombosis and Haemostasis, ISSN 1538-7933, E-ISSN 1538-7836, Vol. 14, no 3, p. 531-545Article in journal (Refereed)
    Abstract [en]

    The lectin pathway's MASP-1/2 activates coagulation factors but the trigger of the activation is unknown. MASP-1/2 activation was assessed by quantifying complexes between MASPs and antithrombin/C1-inhibitor. Activated platelets and fibrin were demonstrated to activate MASP-1 and MASP-2 both invitro and invivo. These findings may represent a crossroad between the complement and the coagulation systems. Summary Background The activated forms of the complement lectin pathway (LP) proteases MASP-1 and MASP-2 are able to cleave the coagulation factors prothrombin, fibrinogen, factor XIII and thrombin-activatable fibrinolysis inhibitor invitro. In vivo studies also show that MASP-1 is involved in thrombogenesis. Objectives To clarify the not yet identified mechanisms involved in triggering activation of the LP during thrombotic reactions. Methods Novel sandwich-ELISAs for detection of complexes between MASP-1 or MASP-2 and the serpins C1 inhibitor (C1-INH) or antithrombin (AT), were used to specifically detect and quantify the activated forms of MASP-1 and MASP-2. Results Activated platelets were shown by flow cytometry to bind Ficolin-1, -2 and -3 but not MBL, which was associated with activation of MASP-1 and MASP-2. We also demonstrated that fibrin and the plasmin-generated fibrin fragment DD in plasma, bind and activate MASP-1 and MASP-2. As demonstrated by the ELISA and SDS-PAGE/Western blotting, the fibrin-associated activation was reflected in a specific inactivation by AT during clotting without the assistance of heparin. In all other cases the MASPs were, as previously reported, inactivated by C1-INH. In systemic lupus erythematosus patients with thrombotic disease and in polytrauma patients, the levels of activated MASP-1 and MASP-2 in complex with both AT and C1-INH were associated with markers of thrombotic disease and contact/coagulation system activation. Conclusions MASP-1 and MASP-2 are activated during blood clotting. This activation is triggered by activated platelets and by the generation of fibrin during thrombotic reactions invitro and invivo, and may represent a novel activation/amplification mechanism in thromboinflammation.

  • 28. Kruse, Robert
    et al.
    Säve, Susanne
    Linnaeus University, Faculty of Science and Engineering, School of Natural Sciences.
    Persson, Katarina
    Linnaeus University, Faculty of Science and Engineering, School of Natural Sciences.
    Adenosine Triphosphate Induced P2Y(2) Receptor Activation Induces Proinflammatory Cytokine Release in Uroepithelial Cells.2012In: Journal of Urology, ISSN 0022-5347, E-ISSN 1527-3792, Vol. 188, no 6, p. 2419-2425Article in journal (Refereed)
    Abstract [en]

    PURPOSE: We characterized and identified the uroepithelial P2 receptor responsible for adenosine triphosphate mediated release of the cytokines interleukin-8 and 6.

    MATERIALS AND METHODS: The human renal epithelial cell line A498 (ATCC™) was cultured and stimulated with different purinergic agonists with or without prior inhibition with different antagonists or signaling pathway inhibitors. Supernatant was analyzed for interleukin-8 and 6 by enzyme-linked immunosorbent assay. P2 receptor mRNA expression was assessed by real-time reverse transcriptase-polymerase chain reaction. The candidate receptor was knocked down with siRNA technology. Interleukin-8 and 6 responses were measured after purinergic stimulation of knocked down cells.

    RESULTS: ATP and ATP-γ-S (Roche Diagnostics, Mannheim, Germany) were equipotent as inducers of interleukin-8 and 6 release. Agonist profile experiments using different P2 receptor agonists indicated that P2Y(2) was the main contributor to this release, although P2Y(11) and P2X(7) activation could not be excluded. Signaling pathway experiments showed that interleukin-8 release involved phospholipase C and inositol trisphosphate mediated signaling, indicating a P2Y receptor subtype. Antagonist experiments indicated P2Y(2) as the responsible receptor. Gene expression analysis of P2 receptors showed that strong expression of P2Y(2) receptor and subsequent knockdown of P2Y(2) receptor mRNA for 72 and 96 hours abrogated interleukin-8 and 6 release after purinergic stimulation with adenosine triphosphate-γ-S.

    CONCLUSIONS: Interleukin-8 and 6 release after purinergic stimulation in uroepithelial A498 cells is mediated through P2Y(2) receptor activation.

  • 29. Kuraya, M
    et al.
    Nilsson, B
    Nilsson Ekdahl, Kristina
    Department of Clinical Immunology and Transfusion Medicine, University Hospital, Uppsala.
    Klein, E
    C3d-mediated negative and positive signals on the proliferation of human B cells separated from blood1990In: Immunology Letters, ISSN 0165-2478, E-ISSN 1879-0542, Vol. 26, no 1, p. 51-58Article in journal (Refereed)
    Abstract [en]

    Soluble C3d applied to human blood-derived B lymphocytes inhibited anti-μ, T cell-produced growth factor, and EBV-induced DNA synthesis in serum-free culture. C3d added to the B cell cultures 1 and 2 days after the stimulus, still exerted inhibition, though with gradually diminishing efficiency.

    C3d, fixed on zymosan or attached to the culture wells, induced [3H]thymidine incorporation of the B cells in serum-free medium. The concentration of C3d used to coat the wells was critical, with optimal stimulatory effect of 8.3 μg/ml. These C3d molecules were shown to be denatured.

    Our results are in line with earlier data on B cells derived from mouse spleen and human tonsils showing that depending on the way of presentation and its amounts, the natural ligand of CR2 can exert negative or positive signals. Moreover, we demonstrate that C3d can inhibit even the proliferative stimulus of EBV. 

  • 30. Lavö, B
    et al.
    Nilsson, B
    Lööf, L
    Nilsson, U R
    Nilsson Ekdahl, Kristina
    Department of Clinical Immunology and Transfusion Medicine, University Hospital, Uppsala.
    Fc receptor function and circulating immune complexes in gluten sensitive enteropathy - possible significance of serum IgA1991In: Gut, ISSN 0017-5749, E-ISSN 1468-3288, Vol. 32, p. 876-880Article in journal (Refereed)
    Abstract [en]

    The capacity to clear IgG containing immune complexes from the circulation was studied in patients with coeliac disease (n = 13), dermatitis herpetiformis (n = 8), and coeliac disease with concomitant serum IgA deficiency (n = 4). A small group of patients with active ulcerative colitis (n = 4) was included as a bowel disease control group. Clearance was estimated by measuring the disappearance rate of a bolus dose of intravenously injected IgG coated autologous erythrocytes. The mean T1/2 of clearance was prolonged in both coeliac disease (86 (24) minutes) and dermatitis herpetiformis (111 (35) minutes), compared with healthy subjects (20 (5) minutes) and coeliac patients with concomitant serum IgA deficiency (T1/2 = 17 (6) minutes). Patients with ulcerative colitis had a prolonged clearance, with a T1/2 of 195 (63) minutes. Values of circulating immune complexes were measured by four assays; C1q binding and C3, IgG, and IgA containing immune complexes. C1q binding immune complexes were detected only in IgA deficient gluten sensitive enteropathy. Patients with coeliac disease and dermatitis herpetiformis had higher values of C3, IgG, and IgA containing immune complexes than control subjects and serum IgA deficient patients with coeliac disease. The clearance rate was inversely correlated to the amount of immune complexes for the subgroups of gluten sensitive enteropathy. 

  • 31.
    Lindblom, Rickard P. F.
    et al.
    Karolinska Institutet ; Uppsala University.
    Aeinehband, Shainn
    Karolinska Institutet.
    Ström, Mikael
    Karolinska Institutet.
    Al Nimer, Faiez
    Karolinska Institutet.
    Sandholm, Kerstin
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Khademi, Mohsen
    Karolinska Institutet.
    Nilsson, Bo
    Uppsala University.
    Piehl, Fredrik
    Karolinska Institutet.
    Nilsson Ekdahl, Kristina
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences. Uppsala University.
    Complement receptor 2 is increased in cerebrospinal fluid of multiple sclerosis patients and regulates C3 function2016In: Clinical Immunology, ISSN 1521-6616, E-ISSN 1521-7035, Vol. 166, p. 89-95Article in journal (Refereed)
    Abstract [en]

    Besides its vital role in immunity, the complement system also contributes to the shaping of the synaptic circuitry of the brain. We recently described that soluble Complement Receptor 2 (sCR2) is part of the nerve injury response in rodents. We here study CR2 in context of multiple sclerosis (MS) and explore the molecular effects of CR2 on C3 activation.

    Significant increases in sCR2 levels were evident in cerebrospinal fluid (CSF) from both patients with relapsing-remitting MS (n = 33; 6.2 ng/mL) and secondary-progressive MS (n = 9; 7.0 ng/mL) as compared to controls (n = 18; 4.1 ng/mL). Furthermore, CSF sCR2 levels correlated significantly both with CSF C3 and C1q as well as to a disease severity measure. In vitro, sCR2 inhibited the cleavage and down regulation of C3b to iC3b, suggesting that it exerts a modulatory role in complement activation downstream of C3.

    These results propose a novel function for CR2/sCR2 in human neuroinflammatory conditions.

  • 32.
    Lindblom, Rickard P. F.
    et al.
    Karolinska Institutet ; Univ Uppsala Hosp ; Karolinska Univ Hosp.
    Berg, Alexander
    Karolinska Institutet.
    Ström, Mikael
    Karolinska Institutet.
    Aeinehband, Shahin
    Karolinska Institutet.
    Dominguez, Cecilia A.
    Karolinska Institutet.
    Al Nimer, Faiez
    Karolinska Institutet.
    Abdelmagid, Nada
    Karolinska Institutet.
    Heinig, Matthias
    Max Delbruck Ctr Mol Med, Germany.
    Zelano, Johan
    Karolinska Institutet.
    Harnesk, Karin
    Karolinska Institutet.
    Hubner, Norbert
    Max Delbruck Ctr Mol Med, Germany.
    Nilsson, Bo
    Uppsala University.
    Nilsson Ekdahl, Kristina
    Uppsala University.
    Diez, Margarita
    Karolinska Institutet.
    Cullheim, Staffan
    Karolinska Institutet.
    Piehl, Fredrik
    Karolinska Institutet.
    Complement receptor 2 is up regulated in the spinal cord following nerve root injury and modulates the spinal cord response2015In: Journal of Neuroinflammation, ISSN 1742-2094, E-ISSN 1742-2094, Vol. 12, article id 192Article in journal (Refereed)
    Abstract [en]

    Background: Activation of the complement system has been implicated in both acute and chronic states of neurodegeneration. However, a detailed understanding of this complex network of interacting components is still lacking. Methods: Large-scale global expression profiling in a rat F2(DAxPVG) intercross identified a strong cis-regulatory influence on the local expression of complement receptor 2 (Cr2) in the spinal cord after ventral root avulsion (VRA). Expression of Cr2 in the spinal cord was studied in a separate cohort of DA and PVG rats at different time-points after VRA, and also following sciatic nerve transection (SNT) in the same strains. Consequently, Cr2(-/-) mice and Wt controls were used to further explore the role of Cr2 in the spinal cord following SNT. The in vivo experiments were complemented by astrocyte and microglia cell cultures. Results: Expression of Cr2 in naive spinal cord was low but strongly up regulated at 5-7 days after both VRA and SNT. Levels of Cr2 expression, as well as astrocyte activation, was higher in PVG rats than DA rats following both VRA and SNT. Subsequent in vitro studies proposed astrocytes as the main source of Cr2 expression. A functional role for Cr2 is suggested by the finding that transgenic mice lacking Cr2 displayed increased loss of synaptic nerve terminals following nerve injury. We also detected increased levels of soluble CR2 (sCR2) in the cerebrospinal fluid of rats following VRA. Conclusions: These results demonstrate that local expression of Cr2 in the central nervous system is part of the axotomy reaction and is suggested to modulate subsequent complement mediated effects.

  • 33. Lundgren, Brita A
    et al.
    Rorsman, Fredrik
    Portela-Gomes, G
    Grimelius, Lars
    Nilsson Ekdahl, Kristina
    Linnaeus University, Faculty of Science and Engineering, School of Natural Sciences.
    Nilsson, Bo
    Ekwall, Olof
    Identification of complement C3 as an autoantigen in inflammatory bowel disease2010In: Journal of Gastroenterology and Hepatology, ISSN 0815-9319, E-ISSN 1440-1746, Vol. 2, no 4, p. 429-436Article in journal (Refereed)
  • 34.
    Mahmoudi, Maryam
    et al.
    Teheran University of Medical Sciences, Iran.
    Nilsson, Per H.
    University of Oslo, Norway ; Oslo University Hospital, Rikshospitalet, Norway.
    Mollnes, Tom Eirik
    Oslo University Hospital, Rikshospitalet, Norway ; University of Oslo, Norway ; Nordland Hospital, Norway.
    Roos, Dirk
    University of Amsterdam, The Netherlands.
    Sullivan, Kathleen E.
    University of Pennsylvania, USA.
    Complement Deficiencies2017In: Primary Immunodeficiency Diseases: Definition, Diagnosis, and Management / [ed] Rezaei, Nima; Aghamohammadi, Asghar; Notarangelo, Luigi D, Berlin, Heidelberg: Springer, 2017, 2nd, p. 437-460Chapter in book (Refereed)
  • 35.
    Mohlin, Camilla
    et al.
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Sandholm, Kerstin
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Kvanta, Anders
    Karolinska institutet.
    Nilsson Ekdahl, Kristina
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences. Uppsala university.
    Johansson, Kjell
    Örebro university.
    A model to study complement involvement in experimental retinal degeneration.2018In: Upsala Journal of Medical Sciences, ISSN 0300-9734, E-ISSN 2000-1967, Vol. 123, no 1, p. 28-42Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: The complement system (CS) plays a role in the pathogenesis of a number of ocular diseases, including diabetic retinopathy (DR), glaucoma, uveitis, and age-related macular degeneration (AMD). Given that many of the complex eye-related degenerative diseases have limited treatment opportunities, we aimed to mimic the in vivo retinal degenerative process by developing a relevant co-culture system.

    METHOD AND MATERIALS: The adult porcine retina was co-cultured with the spontaneously arising human retinal pigment epithelial cells-19 (ARPE-19).

    RESULTS: Inflammatory activity was found after culture and included migrating microglial cells, gliosis, cell death, and CS activation (demonstrated by a minor increase in the secreted anaphylotoxin C3a in co-culture). CS components, including C1q, C3, C4, soluble C5b-9, and the C5a receptor, were expressed in the retina and/or ARPE cells after culture. C1q, C3, and CS regulators such as C4 binding protein (C4BP), factor H (CFH), and factor I (CFI) were secreted after culture.

    DISCUSSION: Thus, our research indicates that this co-culturing system may be useful for investigations of the CS and its involvement in experimental neurodegenerative diseases.

  • 36.
    Momeni, Naghi
    et al.
    Linnaeus University, Faculty of Science and Engineering, School of Natural Sciences.
    Brudin, Lars
    Kalmar County Hospital.
    Behnia, Fatemeh
    University of Social Welfare and rehabilitation Sciences, Iran.
    Nordström, Berit
    Lund University.
    Yousefi-Oudarji, Ali
    Tehran University of Medical Sciences, Iran.
    Sivberg, Bengt
    Lund University.
    Joghataei, Mohammad
    Tehran University of Medical Sciences, Iran.
    Persson, Bengt L.
    Linnaeus University, Faculty of Science and Engineering, School of Natural Sciences.
    High complement factor I activity in the plasma of children with autism spectrum disorders2012In: Autism Research and Treatment, ISSN 2090-1925, E-ISSN 2090-1933, article id 868576Article in journal (Refereed)
    Abstract [en]

    Autism spectrum disorders (ASDs) are neurodevelopmental and behavioural syndromes affecting social orientation, behaviour, and communication that can be classified as developmental disorders. ASD is also associated with immune system abnormality. Immune system abnormalities may be caused partly by complement system factor I deficiency. Complement factor I is a serine protease present in human plasma that is involved in the degradation of complement protein C3b, which is a major opsonin of the complement system. Deficiency in factor I activity is associated with an increased incidence of infections in humans. In this paper, we show that the mean level of factor I activity in the ASD group is significantly higher than in the control group of typically developed and healthy children, suggesting that high activity of complement factor I might have an impact on the development of ASD.

  • 37. Nilsson, B
    et al.
    Nilsson Ekdahl, Kristina
    Uppsala university.
    Components of the alternative pathway1988In: The Complement System / [ed] K. Rother & G. Till, Springer, 1988, 1, p. 23-49Chapter in book (Other academic)
  • 38. Nilsson, Bo
    et al.
    Korsgren, Olle
    Lambris, John
    Nilsson Ekdahl, Kristina
    Linnaeus University, Faculty of Science and Engineering, School of Natural Sciences.
    Can cells and biomaterials in therapeutic medicine be shielded from innate immune recognition2010In: Trends in immunology, ISSN 1471-4906, E-ISSN 1471-4981, Vol. 31, no 1, p. 32-38Article in journal (Refereed)
    Abstract [en]

    Biomaterials (e.g. polymers, metals, or ceramics), cell and cell cluster (e.g. pancreatic islets) transplantation are beginning to offer novel treatment modalities for some otherwise intractable diseases. The innate immune system is involved in incompatibility reactions that occur when biomaterials or cells are introduced into the blood circulation. In particular, the complement, coagulation and contact systems are involved in the recognition of biomaterials and cells, eliciting activation of platelets and leukocytes. Such treatments are associated with anaphylactoid and thrombotic reactions, inflammation, and rejection of biomaterials and cells, leading to treatment failures and adverse reactions. We discuss here the new technologies that are being developed to shield the biomaterial and cell surfaces from recognition by the innate immune system.

  • 39. Nilsson, Bo
    et al.
    Nilsson Ekdahl, Kristina
    Department of Clinical Immunology and Transfusion Medicine, University Hospital, Uppsala.
    Avila, D
    Nilsson, U R
    Lambris, J D
    Neoantigens in complement component C3 as detected by monoclonal antibodies. Mapping of the recognized epitopes by synthetic peptides1990In: Biochemical Journal, ISSN 0264-6021, E-ISSN 1470-8728, Vol. 268, no 1, p. 55-61Article in journal (Refereed)
    Abstract [en]

    The different fragments of the third complement component, C3, generated upon complement activation/inactivation have the ability to bind to several other complement components and receptors as well as to proteins of foreign origin. These multiple reactivities of C3 fragments are associated with a series of conformational changes occurring in the C3 molecule during its degradation. The conformations acquired by the different C3 fragments are also associated with the exposure of neoantigenic epitopes that are specific for (a) particular fragment(s). In order to study these epitopes and thus the conformational changes occurring in C3, monoclonal antibodies (mAbs) recognizing such epitopes were produced in Balb/c mice after immunization with denatured human C3. Two of the three antibodies (7D84.1 and 7D264.6) presented in this study recognized predominantly surface-bound iC3b, and one mAb (7D323.1) recognized both surface-bound and fluid-phase iC3b. Although none of the mAbs recognized any other fluid-phase C3 fragment, all three antibodies detected micro-titre-plate-fixed C3b and iC3b, but not C3c or C3d. In addition to the reaction with human C3, mAb 7D323.1 also bound to micro-titre-plate-fixed rabbit C3. The epitopes recognized by the three mAbs were further localized by using synthetic peptides that were designed on the basis of the differential binding of the mAbs to the C3 fragments. All three antibodies reacted with C3-(924-965)-peptide, which represents the region of C3 between the kallikrein-cleavage site (923-924) and the elastase-cleavage site (965-966). On the basis of the binding of the mAbs to five different overlapping peptides spanning the region between residues 924 and 965 of the human C3 sequence, and the sequence similarity between human C3 and rabbit C3 within this area, the epitopes recognized by these antibodies are mapped. The contribution of the individual amino acid residues in the formation of the epitopes is discussed. 

  • 40.
    Nilsson, Bo
    et al.
    Uppsala University.
    Nilsson Ekdahl, Kristina
    Uppsala University.
    Kemper, Claudia
    King's College London, UK.
    Mollnes, Tom Eirik
    Nordland Hospital, Norway ; University of Tromsø, Norway.
    Preface2015In: Molecular Immunology, ISSN 0161-5890, E-ISSN 1872-9142, Vol. 67, no 1, p. 1-2Article in journal (Other academic)
  • 41.
    Nilsson, Bo
    et al.
    Uppsala University.
    Nilsson Ekdahl, Kristina
    Uppsala University.
    Kemper, Claudia
    King's College London, UK.
    Mollnes, Tom Eirik
    Nordland Hospital, Norway;University of Tromsø, Norway.
    Preface. 15th European Meeting on Complement in Human Disease 2015, Uppsala, Sweden.2015In: Molecular Immunology, ISSN 0161-5890, E-ISSN 1872-9142, Vol. 67, no 1, p. 1-2Article in journal (Other academic)
  • 42. Nilsson, Bo
    et al.
    Nilsson Ekdahl, Kristina
    Department of Clinical Immunology and Transfusion Medicine, University Hospital, Uppsala.
    Svarvare, M
    Bjelle, A
    Nilsson, U R
    Purification and characterization of IgG immunoconglutinins from patients with systemic lupus erythematosus: Implications for a regulatory function1990In: Clinical and Experimental Immunology, ISSN 0009-9104, E-ISSN 1365-2249, Vol. 82, no 2, p. 262-267Article in journal (Refereed)
    Abstract [en]

    The levels of IgG immunoconglutinins in plasma from patients with rheumatoid arthritis, systemic lupus erythematosus and primary biliary cirrhosis were monitored by ELISA. High levels of IgG immunoconglutinins were found mainly in plasma from patients with systemic lupus erythematosus. These immunoconglutinins bound to microtitre plate-fixed C3, C3b and C3c but poorly to C3d. This binding was inhibited by particle-bound C3b and iC3b but not by the corresponding soluble fragments. Furthermore, Western blot analysis revealed no immunoconglutinin-binding to reduced C3 peptides and no binding was shown to soluble C3 α and β chain by ELISA. IgG immunoconglutinins were purified from three plasma specimens by affinity chromatography on activated thiol sepharose ATS/C3 fragments. Two immunoconglutinin preparations that preferentially recognize ATS-C3b, inhibited C5-converlase function by 50–100% while one immunoconglutinin that recognized ATS-C3d,g had no effect. The two former immunoconglutinins also inhibited all three factor I cleavages in C3α chain but the latter inhibited only the third cleavage. None of the immunoconglutinins affected the binding of complement-coated anti-BSA/BSA complexes to CRI (CD 35) on human erythrocytes, but the two immunoconglutinins that inhibited all factor I cleavages also inhibited the factor I-induced release of anti-BSA/BSA complexes from CRI. The results show that immunoconglutinins recognize specific epitopes on bound C3 fragments and that they are able to modulate C3-mcdiated functions. 

  • 43. Nilsson, Bo
    et al.
    Nilsson Ekdahl, Kristina
    Department of Clinical Immunology and Transfusion Medicine, University Hospital, Uppsala.
    Svensson, K E
    Bjelle, A
    Nilsson, U R
    Distinctive expression of neoantigenic C3(D) epitopes on bound C3 following activation and binding to different target surfaces in normal and pathological human sera1989In: Molecular Immunology, ISSN 0161-5890, E-ISSN 1872-9142, Vol. 26, no 4, p. 383-390Article in journal (Refereed)
    Abstract [en]

    Binding of C3 to sheep erythrocytes in a serum-free milieu (EAC14oxy2, EAC142) has previously been shown to mimic the antigenic change that occurs upon denaturation of C3 in sodium dodecyl sulphate (SDS), whereby neoantigenic C3(D) epitopes are exposed. The present paper deals with C3 bound to various target surfaces which are known to modulate the functional properties of C3 in different ways. Bound C3 fragments on serum-treated human aggregated gammaglobulin, zymosan, rabbit and sheep erythrocytes, and on circulating immune complexes isolated from sera of patients with rheumatoid arthritis and systemic lupus erythematosus, were shown to be mainly in the iC3b form. By RIAs, employing polyclonal antibodies, the range of C3(D) antigenic epitopes of 125I-labelled SDS denatured C3 expressed by the particle-bound iC3b was monitored. The physiologically bound iC3b on all tested particles expressed wide ranges of C3(D) epitopes and each type of particle-bound C3 exposed its individual range. By competition ELISA specific C3(D)α epitopes were monitored, employing monoclonal antibodies. A distinct difference in the expression of these epitopes was observed in iC3b bound to various test particles in the presence of normal serum and in iC3b present on circulating immune complexes from pathological sera. Considering that the neoantigenic C3(D) epitopes have been shown to be associated with different functions of C3, the distinctive antigenic expression of each type of serum-treated particle might reflect different functional forms of the protein. 

  • 44.
    Nilsson Ekdahl, Kristina
    Department of Medical and Physiological Chemistry, University of Uppsala.
    In vitro phosphorylation of fructose-1,6-bisphosphatase from rabbit and pig liver with cyclic AMP-dependent protein kinase1988In: Archives of Biochemistry and Biophysics, ISSN 0003-9861, E-ISSN 1096-0384, Vol. 262, no 1, p. 27-31Article in journal (Refereed)
    Abstract [en]

    Homogeneous preparations of fructose-1,6-bisphosphatase from mouse, man, rabbit, pig, and rat were tested as substrates for cyclic AMP-dependent protein kinase. Up to 1 mol of [32P]phosphate per mole enzyme subunit was incorporated into fructose-1,6-bisphosphatase from pig and rabbit liver, which should be compared with 2.6 mol of phosphate per mole enzyme subunit in the case of the rat liver enzyme. The phosphorylation of fructose-1,6-bisphosphatase from the livers of man and mouse was negligible. Phosphorylation of pig and rabbit fructose-1,6-bisphosphatase decreased the apparent Km for fructose-1,6-bisphosphate, but in contrast to the case of the rat liver enzyme it did not change the inhibition constants for AMP and fructose-2,6-bisphosphate. The Phosphorylation sites in rabbit and pig liver fructose-1,6-bisphosphatase were located close to the carboxyterminal of the polypeptide chains, since trypsin treatment of the phosphorylated enzyme quantitatively removed all of the protein-bound radioactivity without significantly altering the subunit molecular weight and with a maintained neutral pH Optimum. 

  • 45.
    Nilsson Ekdahl, Kristina
    Department of Medical and Physiological Chemistry, Biomedical Center, University of Uppsala.
    Rat liver fructose-1,6-bisphosphatase: Identification of serine- 338 as a third major phosphorylation site for cyclic AMP-dependent protein kinase. Activity changes associated with multisite phosphorylation in vitro1987In: Journal of Biological Chemistry, ISSN 0021-9258, E-ISSN 1083-351X, Vol. 262, p. 16699-16703Article in journal (Refereed)
    Abstract [en]

    Rat liver fructose-1,6-bisphosphatase was phosphorylated with [32P]ATP and the catalytic subunit of cyclic AMP-dependent protein kinase. After digestion with trypsin, two peptides were isolated containing 68 and 32% of the total radioactivity, respectively. The former was found to contain the sequence Ala-Lys-Ser(P)-Arg-Pro-Ser(P)-Leu-Pro. In this fragment, Ser-341, but not Ser-338, had earlier been reported to be a phosphorylation site. The other peptide contained phosphorylated Ser-356. It was demonstrated that all the protein-bound [32P]phosphate was distributed evenly between these three serines in the native enzyme regardless of the degree of phosphorylation. Preservation of the three-dimensional structure, however, was needed to obtain phosphorylation of Ser-356. Peptides containing each phosphorylatable serine residue were sequentially removed by digesting the enzyme with chymotrypsin which cleaved off Ser-356, denaturing it with urea, digesting it further with chymotrypsin, thus removing Ser-341, and finally treating it with trypsin which eliminated the rest of the radioactivity which was bound to Ser-338. Kinetic studies of fructose-1,6-bisphosphatase digested in this manner revealed that phosphorylation of Ser-338 decreased the apparent Km for fructose 1,6-bisphosphatase, whereas phosphorylation of Ser-341 decreased the inhibitory effect of AMP and fructose 2,6-bisphosphatase, Phosphorylation of Ser-356 did not affect these parameters. 

  • 46.
    Nilsson Ekdahl, Kristina
    Uppsala University.
    Studies on the regulation of rat liver pyruvate kinase and fructose 1,6-bisphosphatase1987Doctoral thesis, comprehensive summary (Other academic)
  • 47.
    Nilsson Ekdahl, Kristina
    Department of Medical and Physiological Chemistry, Biomedical Center, University of Uppsala.
    Studies on the regulation of rat liver pyruvate kinase and fructose-1,6-bisphosphatase1987In: Upsala journal of medical sciences, Vol. 92, no 3, p. 217-232Article in journal (Refereed)
  • 48.
    Nilsson Ekdahl, Kristina
    et al.
    Department of Medical and Physiological Chemistv, University of Uppsala, Box 575, S-75123 Uppsala, Sweden.
    Ekman, P
    Fructose-1,6-bisphosphatase from rat liver. A comparison of the kinetics of the unphosphorylated enzyme and the enzyme phosphorylated by cyclic AMP-dependent protein kinase.1985In: Journal of Biological Chemistry, ISSN 0021-9258, E-ISSN 1083-351X, Vol. 260, p. 14173-14179Article in journal (Refereed)
    Abstract [en]

    A purification procedure for rat hepatic fructose-1,6-bisphosphatase, described earlier, has been improved, resulting in an enzyme preparation with a neutral pH optimum and with both phosphorylatable serine residues present. The subunit Mr was 40,000. Phosphorylation in vitro with cyclic AMP-dependent protein kinase resulted in the incorporation of 1.4 mol of phosphate/mol of subunit and led to an almost 2-fold decrease in apparent Km for fructose-1,6-bisphosphate. In contrast to yeast fructose-1,6-bisphosphatase, fructose-2,6-bisphosphate had no effect on the rate of phosphorylation or dephosphorylation of the intact enzyme. The effects of the composition of the assay medium, with regard to buffering substance and Mg2+ concentration, on the apparent Km values of phosphorylated and unphosphorylated enzyme were investigated. The kinetics of phosphorylated and unphosphorylated fructose-1,6-bisphosphatase were studied with special reference to the inhibitory effects of adenine nucleotides and fructose-2,6-bisphosphate. Unphosphorylated fructose-1,6-bisphosphatase was more susceptible to inhibition by both AMP and fructose 2,6-bisphosphate than phosphorylated enzyme, at high and low substrate concentrations. Both ATP and ADP had a similar effect on the two enzyme forms, ADP being the more potent inhibitor. Finally, the combined effect of several inhibitors at physiological concentrations was studied. Under conditions resembling the gluconeogenic state, phosphorylated fructose-1,6-bisphosphatase was found to have twice the activity of the unphosphorylated enzyme. 

  • 49.
    Nilsson Ekdahl, Kristina
    et al.
    UNIV UPPSALA, CTR BIOMED, DEPT CIENCIAS BIOL, S-75123 UPPSALA, SWEDEN .
    Ekman, P
    Hepatic L-type pyruvate kinase: Separation of unphosphorylated, phosphorylated and proteolytically modified in vivo forms1984In: Journal of Biochemistry (Tokyo), ISSN 0021-924X, E-ISSN 1756-2651, Vol. 95, no 4, p. 917-924Article in journal (Refereed)
  • 50.
    Nilsson Ekdahl, Kristina
    et al.
    Department of Medical and Physiological Chemistry, Biomedical Center, University of Uppsala .
    Ekman, Pia
    Department of Medical and Physiological Chemistry, Biomedical Center, University of Uppsala.
    Effects of epinephrine, glucagon and insulin on the activity and degree of phosphorylation of fructose-1,6-bisphosphatase in cultured hepatocytes1987In: Biochimica et Biophysica Acta. Molecular Cell Research, ISSN 0167-4889, E-ISSN 1879-2596, Vol. 929, p. 318-326Article in journal (Refereed)
    Abstract [en]

    The effects of epinephrine, glucagon and insulin on the activity and degree of phosphorylation of fructose-1,6-bisphosphatase in isolated hepatocytes maintained in cell culture for 24 h were investigated. Epinephrine caused a rapid decrease in the apparent Km monitored as the activity ratio between the activity at 12.5 and 83 μM fructose-1,6-bisphosphate, reaching a maximum after 5 min. Glucagon caused a slower and less pronounced activation, and insulin caused an equally slow increase in Km. The effect of epinephrine and glucagon was completely reciprocated by insulin and the action of insulin was totally erased by the other two. Glucagon stimulated the incorporation of [32P]phosphate into fructose-1,6-bisphosphatase from about 2.5 to 4.2 mol/mol enzyme and epinephrine to 3.5 mol/mol. The effect of the two hormones acting together was cumulative. Insulin brought about a decrease in the degree of phosphorylation to 2.0 mol/mol. The effect of epinephrine was shown to be caused by the β-receptors, since it was completely blocked by propanolol (a β-antagonist) and remained unaffected by the presence of phentolamine (an α-antagonist). 

12 1 - 50 of 76
CiteExportLink to result list
Permanent link
Cite
Citation style
  • apa
  • harvard1
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf