lnu.sePublications
Change search
Refine search result
12345 1 - 50 of 204
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.
    Aeinehband, Shahin
    et al.
    Karolinska Institutet.
    Lindblom, Rickard P. F.
    Karolinska Institutet.
    Al Nimer, Faiez
    Karolinska Institutet.
    Vijayaraghavan, Swetha
    Karolinska Institutet.
    Sandholm, Kerstin
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Khademi, Mohsen
    Karolinska Institutet.
    Olsson, Tomas
    Karolinska Institutet.
    Nilsson, Bo
    Uppsala University.
    Nilsson Ekdahl, Kristina
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences. Uppsala University.
    Darreh-Shori, Taher
    Karolinska Institutet.
    Piehl, Fredrik
    Karolinska Institutet.
    Complement Component C3 and Butyrylcholinesterase Activity Are Associated with Neurodegeneration and Clinical Disability in Multiple Sclerosis2015In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 10, no 4, article id e0122048Article in journal (Refereed)
    Abstract [en]

    Dysregulation of the complement system is evident in many CNS diseases but mechanisms regulating complement activation in the CNS remain unclear. In a recent large rat genomewide expression profiling and linkage analysis we found co-regulation of complement C3 immediately downstream of butyrylcholinesterase (BuChE), an enzyme hydrolyzing acetylcholine (ACh), a classical neurotransmitter with immunoregulatory effects. We here determined levels of neurofilament-light (NFL), a marker for ongoing nerve injury, C3 and activity of the two main ACh hydrolyzing enzymes, acetylcholinesterase (AChE) and BuChE, in cerebrospinal fluid (CSF) from patients with MS (n = 48) and non-inflammatory controls (n = 18). C3 levels were elevated in MS patients compared to controls and correlated both to disability and NFL. C3 levels were not induced by relapses, but were increased in patients with >= 9 cerebral lesions on magnetic resonance imaging and in patients with progressive disease. BuChE activity did not differ at the group level, but was correlated to both C3 and NFL levels in individual samples. In conclusion, we show that CSF C3 correlates both to a marker for ongoing nerve injury and degree of disease disability. Moreover, our results also suggest a potential link between intrathecal cholinergic activity and complement activation. These results motivate further efforts directed at elucidating the regulation and effector functions of the complement system in MS, and its relation to cholinergic tone.

  • 2. 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. 

  • 3. 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. 

  • 4. 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)
  • 5. Alston-Smith, J
    et al.
    Ware, J
    Ljungqvist, O
    Nilsson Ekdahl, Kristina
    University of Kalmar, School of Pure and Applied Natural Sciences.
    The effects of hormones and calcium ionophore A23187 on the activity of pyruvate kinase in primary culture and freshly isolated rat hepatocytes1992In: Life science advances, Vol. 11, p. 91-99Article in journal (Refereed)
  • 6. Andersson, J
    et al.
    Bexborn, Fredrik
    University of Kalmar, School of Pure and Applied Natural Sciences.
    Klinth, Jeanna
    University of Kalmar, School of Pure and Applied Natural Sciences.
    Nilsson, B
    Nilsson Ekdahl, Kristina
    University of Kalmar, School of Pure and Applied Natural Sciences.
    Functionalized Pluronic˙ as a linker for immobilization of bioactive molecules on a material surface - a new strategy towards improved biomaterial-blood compatibility2006In: Journal of biomedical materials research, Vol. 76A, no 1, p. 25-34Article in journal (Refereed)
  • 7. Andersson, J
    et al.
    Larsson, R
    Richter, R
    Nilsson Ekdahl, Kristina
    University of Kalmar, School of Pure and Applied Natural Sciences.
    Nilsson, B
    Binding of a model regulator of complement activation (RCA) to a biomaterial surface: Surface-bound factor H inhibits complement activation2001In: Biomaterials, Vol. 22 (17), p. 2435-2443Article in journal (Refereed)
  • 8. Andersson, J
    et al.
    Nilsson Ekdahl, Kristina
    University of Kalmar, School of Pure and Applied Natural Sciences.
    Lambris, J D
    Nilsson, Bo
    Complement activation on a model biomaterial surface: Binding of C3b via the alternative amplification loop to plasma proteins adsorbed to the surface2005In: Biomaterials, Vol. 26 (13), p. 1477-1485Article in journal (Refereed)
  • 9. Andersson, J
    et al.
    Nilsson Ekdahl, Kristina
    University of Kalmar, School of Pure and Applied Natural Sciences.
    Larsson, R
    Nilsson, U R
    Nilsson, B
    C3 adsorbed to a polymer surface can form an initiating alternative pathway convertase2002In: Journal of immunology, Vol. 168, p. 5786-5791Article in journal (Refereed)
  • 10. Andersson, J
    et al.
    Sanchez, J
    Nilsson Ekdahl, Kristina
    University of Kalmar, School of Pure and Applied Natural Sciences.
    Elgue, G
    Nilsson, B
    Larsson, R
    Optimal heparin surface concentration and antithrombin binding capacity as evaluated with human non-anticoagulated blood in vitro2003In: Journal of biomedical materials research, Vol. 67A (2), p. 458-466Article in journal (Refereed)
  • 11.
    Asif, Sana
    et al.
    Uppsala University.
    Jonsson, Nina
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences. Uppsala University.
    Teramura, Yuji
    Univ Tokyo, Japan.
    Gustafson, Elisabet
    Univ Uppsala Hosp.
    Nilsson Ekdahl, Kristina
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences. Uppsala University.
    Nilsson, Bo
    Uppsala University.
    Conjugation of human recombinant CD39 to primary human hepatocytes protects against thromboinflammation2015In: Xenotransplantation, ISSN 0908-665X, E-ISSN 1399-3089, Vol. 22, p. S87-S87Article in journal (Other academic)
  • 12.
    Asif, Sana
    et al.
    Uppsala University.
    Nilsson Ekdahl, Kristina
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences. Uppsala University.
    Fromell, Karin
    Uppsala University.
    Gustafson, Elisabet
    Uppsala University Hospital.
    Barbu, Andreea
    Uppsala University.
    Le Blanc, Katarina
    Karolinska Institutet ; Karolinska University Hospital.
    Nilsson, Bo
    Uppsala University.
    Teramura, Yuji
    Uppsala University ; The University of Tokyo, Japan.
    Heparinization of cell surfaces with short peptide-conjugated PEG-lipid regulates thromboinflammation in transplantation of human MSCs and hepatocytes2016In: Acta Biomaterialia, ISSN 1742-7061, E-ISSN 1878-7568, Vol. 35, p. 194-205Article in journal (Refereed)
    Abstract [en]

    Infusion of therapeutic cells into humans is associated with immune responses, including thromboinflammation, which result in a large loss of transplanted cells\ To address these problems, heparinization of the cell surfaces was achieved by a cell-surface modification technique using polyethylene glycol conjugated phospholipid (PEG-lipid) derivatives. A short heparin-binding peptide was conjugated to the PEG-lipid for immobilization of heparin conjugates on the surface of human mesenchymal stem cells (hMSCs) and human hepatocytes. Here three kinds of heparin-binding peptides were used for immobilizing heparin conjugates and examined for the antithrombogenic effects on the cell surface. The heparinized cells were incubated in human whole blood to evaluate their hemocompatibility by measuring blood parameters such as platelet count, coagulation markers, complement markers, and Factor Xa activity. We found that one of the heparin-binding peptides did not show cytotoxicity after the immobilization with heparin conjugates. The degree of binding of the heparin conjugates on the cell surface (analyzed by flow cytometer) depended on the ratio of the active peptide to control peptide. For both human MSCs and hepatocytes in whole-blood experiments, no platelet aggregation was seen in the heparin conjugate-immobilized cell group vs. the controls (non-coated cells or control peptide). Also, the levels of thrombin-antithrombin complex (TAT), C3a, and sC5b-9 were significantly lower than those of the controls, indicating a lower activation of coagulation and complement. Factor Xa analysis indicated that the heparin conjugate was still active on the cell surface at 24 h post-coating. It is possible to immobilize heparin conjugates onto hMSC and human hepatocyte surfaces and thereby protect the cell surfaces from damaging thromboinflammation. Statement of Signigficance We present a promising approach to enhance the biocompatibility of therapeutic cells. Here we used short peptide-conjugated PEG-lipid for cell surface modification and heparin conjugates for the coating of human hepatocytes and MSCs. We screened the short peptides to find higher affinity for heparinization of cell surface and performed hemocompatibility assay of heparinized human hepatocytes and human MSCs in human whole blood. Using heparin-binding peptide with higher affinity, not only coagulation activation but also complement activation was significantly suppressed. Thus, it was possible to protect human hepatocytes and human MSCs from the attack of thromboinflammatory activation, which can contribute to the improvement graft survival. (C) 2016 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

  • 13. Babiker, A A
    et al.
    Hamad, O A
    Sanchez, J
    Ronquist, G
    Nilsson, B
    Nilsson Ekdahl, Kristina
    University of Kalmar, School of Pure and Applied Natural Sciences.
    Prothrombotic Effect of Prostasomes of Metastatic Cell and Seminal Origin2007In: The Prostate, ISSN 0270-4137, E-ISSN 1097-0045, Vol. 67, p. 378-388Article in journal (Refereed)
  • 14. Babiker, A A
    et al.
    Nilsson, B
    Ronquist, G
    Carlsson, L
    Nilsson Ekdahl, Kristina
    University of Kalmar, School of Pure and Applied Natural Sciences.
    Transfer of functional prostasomal CD59 of metastatic prostatic cancer cell origin protects cells against complement attack2005In: The prostate, Vol. 62 (2), p. 105-114Article in journal (Refereed)
  • 15. Babiker, A A
    et al.
    Nilsson Ekdahl, Kristina
    University of Kalmar, School of Pure and Applied Natural Sciences.
    Nilsson, B
    Ronquist, G
    Prothrombotic Effects of Prostasomes Isolated from Prostatic Cell Lines and Seminal Plasma2007In: Seminars in Thrombosis and Hemostasis, ISSN 0094-6176, E-ISSN 1098-9064, Vol. 33, p. 80-86Article in journal (Refereed)
  • 16. Babiker, A A
    et al.
    Ronquist, G
    Nilsson, B
    Nilsson Ekdahl, Kristina
    University of Kalmar, School of Pure and Applied Natural Sciences.
    Overexpression of ecto-protein kinases in prostasomes of metastatic origin2006In: Prostate, Vol. 66 (7), p. 675-686Article in journal (Refereed)
  • 17. 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.

  • 18. 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.

  • 19.
    Barbu, Andreea
    et al.
    Uppsala University.
    Hamad, Osama
    Uppsala University.
    Lind, Lars
    Uppsala University.
    Nilsson Ekdahl, Kristina
    Uppsala University.
    Nilsson, Bo
    Uppsala University.
    The role of complement factor C3 in lipid metabolism2015In: Molecular Immunology, ISSN 0161-5890, E-ISSN 1872-9142, Vol. 67, no 1, p. 101-107Article, review/survey (Refereed)
    Abstract [en]

    Abundant reports have shown that there is a strong relationship between C3 and C3a-desArg levels, adipose tissue, and risk factors for cardiovascular disease, metabolic syndrome and diabetes. The data indicate that complement components, particularly C3, are involved in lipid metabolism. The C3 fragment, C3a-desArg, functions as a hormone that has insulin-like effects and facilitates triglyceride metabolism. Adipose tissue produces and regulates the levels of complement components, which promotes generation of inflammatory initiators such as the anaphylatoxins C3a and C5a. The anaphylatoxins trigger a cyto/chemokine response in proportion to the amount of adipose tissue present, and induce inflammation and mediate metabolic effects such as insulin resistance. These observations support the concept that complement is an important participant in lipid metabolism and in obesity, contributing to the metabolic syndrome and to the low-grade inflammation associated with obesity.

  • 20.
    Bergman, Ingrid-Maria
    et al.
    Linnaeus University, Faculty of Science and Engineering, School of Natural Sciences.
    Edman, Kjell
    Linnaeus University, Faculty of Science and Engineering, School of Natural Sciences.
    Nilsson Ekdahl, Kristina
    Linnaeus University, Faculty of Science and Engineering, School of Natural Sciences. Uppsala University.
    Rosengren, K. Johan
    Linnaeus University, Faculty of Science and Engineering, School of Natural Sciences. The University of Queensland, Australia.
    Edfors, Inger
    Linnaeus University, Faculty of Science and Engineering, School of Natural Sciences.
    Extensive polymorphism in the porcine Toll-like receptor 10 gene2012In: International Journal of Immunogenetics, ISSN 1744-3121, E-ISSN 1744-313X, Vol. 39, no 1, p. 68-76Article in journal (Refereed)
    Abstract [en]

    The great importance of the Toll-like receptors (TLRs) in innate immunity is well established, but one family member – TLR10 – remains elusive. TLR10 is expressed in various tissues in several species, but its ligand is not known and its function is still poorly understood. The open reading frame of TLR10 was sequenced in 15 wild boars, representing three populations, and in 15 unrelated domestic pigs of Hampshire, Landrace and Large White origin. Amino acid positions corresponding to detected nonsynonymous single nucleotide polymorphisms (SNPs) were analysed in the crystal structures determined for the human TLR1–TLR2–lipopeptide complex and the human TLR10 Toll/Interleukin 1 receptor (TIR) dimer. SNP occurrence in wild boars and domestic pigs was compared, and haplotypes for the TLR10 gene and the TLR6-1-10 gene cluster were reconstructed. Despite the limited number of animals sequenced in the present study (N = 30), a larger number of SNPs were found in TLR10 than recently reported for TLR1, TLR6 and TLR2. Thirty-three SNPs were detected, of which 20 were nonsynonymous. The relative frequency of nonsynonymous (dN) and synonymous (dS) SNPs between wild boars and domestic pigs was higher in TLR10 than recently reported for TLR1, TLR6 and TLR2. However, the polymorphism reported in the present study seems to leave the function of the TLR10 molecule unaffected. Furthermore, no nonsynonymous SNPs were detected in the part of the gene corresponding to the hinge region of the receptor, probably reflecting rigorously acting functional constraint. The total number of SNPs and the number of nonsynonymous SNPs were significantly lower (< 0.05) in the wild boars than in the domestic pigs, and fewer TLR10 haplotypes were present in the wild boars. The majority of the TLR6-1-10 haplotypes were specific for either wild boars or domestic pigs, probably reflecting differences in microbial environment and population history.

  • 21.
    Bergman, Ingrid-Maria
    et al.
    Linnaeus University, Faculty of Science and Engineering, School of Natural Sciences.
    Sandholm, Kerstin
    Linnaeus University, Faculty of Science and Engineering, School of Natural Sciences.
    Juul-Madsen, Helle R.
    Heegaard, Peter M.
    Nilsson Ekdahl, Kristina
    Linnaeus University, Faculty of Science and Engineering, School of Natural Sciences.
    Edfors, Inger
    Linnaeus University, Faculty of Science and Engineering, School of Natural Sciences.
    MBL-A concentrations and MBL1 genotypes in European wild boars, Large White pigs, and wild boar/Large White crossbreds2010In: 8th European Colloquium on Acute Phase Proteins in Helsinki, 2010.08.25-2010.08.27, 2010, p. 25-26Conference paper (Refereed)
  • 22.
    Bergman, Ingrid-Maria
    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.
    Nilsson Ekdahl, Kristina
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Okumura, Naohiko
    Institute of Society for Techno-innovation of Agriculture, Forestry and Fisheries, Tsukuba, Japan.
    Uenishi, Hirohide
    National Institute of Agrobiological Sciences, Tsukuba, Japan.
    Guldbrandtsen, Bernt
    Aarhus University, Tjele, Denmark.
    Essler, Sabine
    Univ of Veterinary Medicine, Vienna.
    Knoll, Ales
    Mendel University, Brno, Czech Republic.
    Heegaard, Peter
    Technical University of Denmark, Kgs Lyngby.
    Edfors, Inger
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Juul-Madsen, Helle
    Aarhus University, Tjele, Denmark.
    MBL1 genotypes in wild boar populations from Sweden, Austria, the Czech Republic and Japan2013In: International Journal of Immunogenetics, ISSN 1744-3121, E-ISSN 1744-313X, Vol. 40, no 2, p. 131-139Article in journal (Refereed)
    Abstract [en]

    The single nucleotide polymorphism (SNP) G949T in the mannose-binding lectin (MBL) 1 gene has been associated with low MBL-A concentration in serum and detected at different frequencies in various European pig populations. However, the origin of this SNP is not known. Part of the MBL1 gene was sequenced in 12 wild boar/Large White crossbred pigs from the second backcross (BC 2) generation in a family material originating from two wild boar x Large White intercrosses. Also, MBL-A serum concentration was measured in the entire BC 2 generation (n = 45). Furthermore, the genotypes of 68 wild boars from Sweden, Austria, the Czech Republic, and Japan were determined in regard to five previously described SNPs in MBL1. The T allele of G949T was present among the BC 2 animals. MBL-A serum concentration in the BC 2 animals showed a bimodal distribution, with one-third of the animals at levels between 0.7 and 1.6 μg mL−1 and the remaining pigs at levels around 13 μg mL−1. There was a co-variation between the presence of the T allele and low MBL-A concentration in serum. The genotyping of the wild boars revealed differences between populations. The T allele of G949T was not detected in the Austrian and Japanese samples and is thus unlikely to be an original feature of wild boars. In contrast, it was present at high frequency (0.35) among the Swedish wild boars, probably representing a founder effect. Five MBL1 haplotypes were resolved. Only two of these were present among the Japanese wild boars compared to four in each of the European populations. This difference may reflect differences in selection pressure and population history.

  • 23.
    Bexborn, Fredrik
    et al.
    University of Kalmar, School of Pure and Applied Natural Sciences.
    Andersson, P O
    Nilsson Ekdahl, Kristina
    University of Kalmar, School of Pure and Applied Natural Sciences.
    Studies of soluble alternate complement complex formation using fluorescence spectroscopy techniques2006In: Molecular immunology 43 (1-2), 2006Conference paper (Refereed)
  • 24.
    Bexborn, Fredrik
    et al.
    University of Kalmar, School of Pure and Applied Natural Sciences.
    Andersson, Per Ola
    Chen, Hsui
    Nilsson, Bo
    Nilsson Ekdahl, Kristina
    University of Kalmar, School of Pure and Applied Natural Sciences.
    The Tick-Over Theory Revisited: Formation and Regulation of the Soluble Alternative Complement C3 Convertase (C3(H2O)Bb)2008In: Molecular Immunology, ISSN 0161-5890, E-ISSN 1872-9142, Vol. 45, no 8, p. 2370-2379Article in journal (Refereed)
  • 25.
    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.

  • 26. Biglarnia, Ali Reza
    et al.
    Nilsson, Bo
    Nilsson Ekdahl, Kristina
    Linnaeus University, Faculty of Science and Engineering, School of Natural Sciences.
    Tufveson, Gunnar
    Nilsson, Tomas
    Larsson, Erik
    Wadström, Jonas
    Desenzitation Protocol with Antigen-Specific Immunoadsorption Interferes with Complement in ABO Incompatible Renal Transplantation2012In: Transplantation, ISSN 0041-1337, E-ISSN 1534-6080, Vol. 93, no 1, p. 87-92Article, review/survey (Refereed)
    Abstract [en]

    Background. Complement activation was characterized during and after desensitization treatment in 19 consecutive patients receiving ABO-incompatible (ABOi) living donor kidney transplants to assess the effect of desensitization protocol including antigen-specific immunoadsorption (IA) on complement activation.

    Methods. All patients received rituximab- and tacrolimus-based triple treatment. Anti-A/B antibodies were removed by IA. Serial determinations of C3, C3a, the C3a/C3 ratio, and sC5b-9 were carried out between day −30 and postoperative day 30. C1q was measured on day −30 and the day before the transplantation. In two recipients, eluates from immunoadsorbent columns were analyzed for C3a, C1q, and immunoglobulins by western blotting. Same complement analysis was performed in eluate from a control column after in vitro perfusion of AB-plasma.

    Results. Patient and graft survival were 100% for a median follow-up of 40 months (range, 12–60 months). There were no humoral rejections based on ABO-antigen-antibody interactions. C3a and the C3a/C3 ratio declined with the start of IA treatment, and this decline was maintained postoperatively. C1q declined from day −30 to a lower value on the day before transplantation (P<0.05). In eluates from both patient and control, immunoadsorbent column immunoglobulins together with C3a and C1q were detected.

    Conclusions. The current protocol including antigen-specific IA interferes with the complement system; this effect may be partially responsible for the absence of humoral rejection resulting from ABO-antigen-antibody interactions and the excellent outcomes obtained after ABO-incompatible kidney transplantation.

  • 27.
    Biglarnia, Alireza
    et al.
    Uppsala University.
    Nilsson Ekdahl, Kristina
    Uppsala University.
    Nilsson, Bo
    Uppsala University.
    Complement interception across humoral incompatibility in solid organ transplantation: a clinical perspective2015In: Immune Responses to Biosurfaces / [ed] John D. Lambris, Kristina Nilsson-Ekdahl, Daniel Ricklin, Bo Nilsson, Springer, 2015, p. 211-233Chapter in book (Refereed)
    Abstract [en]

    The humoral barrier in transplant biology is the result of preformed donor-specific antibodies (DSAs), directed either against human leukocyte antigens (HLA) or non-HLA antigens such as blood group (ABO) molecules. The term "sensitization" applies to patients carrying these antibodies. Transplantation is widely accepted as a life-saving opportunity for patients with terminal end-organ disease. However, in sensitized patients, transplant outcome is hampered by antibody-mediated rejection (AMR) as a consequence of DSA exposure. Furthermore, sensitized patients have limited access to "matched" organs from the both living and deceased donor pool.Considering the crucial role of the complement system in the pathophysiology of AMR and the availability of complement intervention therapeutics, there is a growing interest in complement-targeting strategies. This review highlights the emerging importance of monitoring and modulation of the complement system in the context of enabling transplantation across humoral incompatibility in sensitized recipients with preformed anti-HLA or natural anti-ABO antibodies. It also discusses the significance of the complement system in the induction of accommodation and further emphasizes current and future perspectives of novel complement therapeutics.

  • 28. 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.

  • 29. 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)
  • 30. Bäck, Jennie
    et al.
    Huber-Lang, Markus
    Elgue, Graciela
    Kalbitz, Miriam
    Sanchez, Javier
    Nilsson Ekdahl, Kristina
    University of Kalmar, School of Pure and Applied Natural Sciences.
    Nilsson, Bo
    Distinctive regulation of contact activation by antithrombin and C1-inhibitor on activated platelets and material surfaces2009In: Biomaterials, ISSN 0142-9612, E-ISSN 1878-5905, Vol. 30, no 34, p. 6573-6580Article in journal (Refereed)
    Abstract [en]

    Activated human plate lets trigger FXII-mediated contactactivation, which leads to the generation of FXIIa–antithrombin (AT) and FXIa–AT complexes. This suggests that contactactivation takes place at different sites, on activatedplatelets and material surfaces, during therapeutic procedures involving biomaterials in contact with blood and is differentially regulated. Here we show that activation in platelet-poor plasma, platelet-rich plasma (PRP), and whole blood induced by glass, kaolin, and polyphosphate elicited high levels of FXIIa-C1-inhibitor (C1INH), low levels of FXIa–C1INH and KK–C1INH, and almost no AT complexes. Plateletactivation, in both PRP and blood, led to the formation of FXIIa–AT, FXIa–AT, and kallikrein (KK)–AT but almost no C1INH complexes. In severe trauma patients, FXIIa–AT and FXIa–AT were correlated with the release of thrombospondin-1 (TSP-1) from activatedplatelets. In contrast, FXIIa–C1INH complexes were detected when the FXIIa–AT levels were low. No correlations were found between FXIIa–C1INH and FXIIa–AT or TSP-1. Inhibition of FXIIa on material surfaces was also shown to affect the function of aggregating platelets. In conclusion, formation of FXIIa–AT and FXIIa–C1INH complexes can help to distinguish between contactactivation triggered by biomaterial surfaces and by activatedplatelets. Platelet aggregation studies also demonstrated that platelet function is influenced by material surface-mediated contactactivation and that generation of FXIIa–AT complexes may serve as a new biomarker for thrombotic reactions during therapeutic procedures employing biomaterial devices.

  • 31.
    Bäck, Jennie
    et al.
    Uppsala University.
    Lood, Christian
    Skåne University Hospital ; Lund University.
    Bengtsson, Anders A.
    Skåne University Hospital ; Lund University.
    Nilsson Ekdahl, Kristina
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences. Uppsala University.
    Nilsson, Bo
    Uppsala University.
    Contact activation products are new potential biomarkers to evaluate the risk of thrombotic events in systemic lupus erythematosus2013In: Arthritis Research & Therapy, ISSN 1478-6354, E-ISSN 1478-6362, Vol. 15, no 6, article id R206Article in journal (Refereed)
    Abstract [en]

    Introduction: Patients with systemic lupus erythematosus (SLE) have persistent platelet activation and an increased risk of thrombotic events, which cannot be accounted for by traditional cardiovascular risk factors. Factor (F)XII has a potentially important role in thrombus formation and is triggered by activated platelets. We therefore asked whether the contact system is involved in inflammation and vascular disease (VD) in SLE. Methods: Fibrin clots were incubated with purified FXII or whole blood, and the activation and regulation of FXII were studied. Plasma from SLE patients with (n = 31) or without (n = 38) previous VD and from matched healthy controls (n = 68) were analyzed for the presence of complexes formed between contact system enzymes and antithrombin (AT) or C1 inhibitor (C1INH) and evaluated with regard to clinical data and laboratory parameters. Results: Fibrin clots elicited FXII activation and acted as co-factors for AT. In clotting plasma, the levels of FXIIa-AT increased, and FXIIa-C1INH decreased. A similar reciprocal relationship existed in SLE patients. FXIIa-AT was elevated in the SLE patients with a history of VD, while the corresponding levels of factor FXIIa-C1INH were significantly decreased. FXIIa-AT correlated strongly with platelet parameters. The odds ratio for VD among the SLE patients was 8.9 if they had low levels of FXIIa-C1INH, 6.1 for those with high levels of FXIIa-AT, and increased to 23.4 for those with both decreased levels of FXIIa-C1INH and increased levels of FXIIa-AT. Conclusions: Activation of FXII is elicited by fibrin during thrombotic reactions in vitro and in vivo, and fibrin acts as a heparin-like co-factor and regulates AT. Patients with SLE had altered levels of FXIIa-serpin complexes, supporting that the contact system is involved in this disease. FXIIa-serpin complexes are strongly associated with previous VD in SLE patients, suggesting that these complexes are potential biomarkers for monitoring and assessing the risk of thrombotic events in SLE.

  • 32. 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.

  • 33.
    Carlsson, Hanna
    et al.
    Kalmar County Hospital.
    Sandholm, Kerstin
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Tjernberg, Ivar
    Kalmar County Hospital.
    Nilsson Ekdahl, Kristina
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences. Uppsala University.
    Complement activation in asymptomatic Lyme borreliosis and neuroborreliosis2015In: Molecular Immunology, ISSN 0161-5890, E-ISSN 1872-9142, Vol. 67, no 1, p. 128-128Article in journal (Other academic)
  • 34.
    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.

  • 35. Darreh-Shori, Taher
    et al.
    Vijayaraghavan, Swetha
    Aeinehband, Shahin
    Piehl, Fredrik
    Lindblom, Rickard P. F.
    Nilsson, Bo
    Nilsson Ekdahl, Kristina
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences. Uppsala Univ, Div Clin Immunol, Dept Immunol Genet & Pathol, Uppsala.
    Langstrom, Bengt
    Almkvist, Ove
    Nordberg, Agneta
    Functional variability in butyrylcholinesterase activity regulates intrathecal cytokine and astroglial biomarker profiles in patients with Alzheimer's disease2013In: Neurobiology of Aging, ISSN 0197-4580, E-ISSN 1558-1497, Vol. 34, no 11, p. 2465-2481Article in journal (Refereed)
    Abstract [en]

    Butyrylcholinesterase (BuChE) activity is associated with activated astrocytes in Alzheimer's disease brain. The BuChE-K variant exhibits 30%-60% reduced acetylcholine (ACh) hydrolyzing capacity. Considering the increasing evidence of an immune-regulatory role of ACh, we investigated if genetic heterogeneity in BuChE affects cerebrospinal fluid (CSF) biomarkers of inflammation and cholinoceptive glial function. Alzheimer's disease patients (n = 179) were BCHE-K-genotyped. Proteomic and enzymatic analyses were performed on CSF and/or plasma. BuChE genotype was linked with differential CSF levels of glial fibrillary acidic protein, S100B, interleukin-1 beta, and tumor necrosis factor (TNF)-alpha. BCHE-K noncarriers displayed 100%-150% higher glial fibrillary acidic protein and 64%-110% higher S100B than BCHE-K carriers, who, in contrast, had 40%-80% higher interleukin-1b and 21%-27% higher TNF-alpha compared with noncarriers. A high level of CSF BuChE enzymatic phenotype also significantly correlated with higher CSF levels of astroglial markers and several factors of the innate complement system, but lower levels of proinflammatory cytokines. These individuals also displayed beneficial paraclinical and clinical findings, such as high cerebral glucose utilization, low beta-amyloid load, and less severe progression of clinical symptoms. In vitro analysis on human astrocytes confirmed the involvement of a regulated BuChE status in the astroglial responses to TNF-alpha and ACh. Histochemical analysis in a rat model of nerve injury-induced neuroinflammation, showed focal assembly of astroglial cells in proximity of BuChE-immunolabeled sites. In conclusion, these results suggest that BuChE enzymatic activity plays an important role in regulating intrinsic inflammation and activity of cholinoceptive glial cells and that this might be of clinical relevance. The dissociation between astroglial markers and inflammatory cytokines indicates that a proper activation and maintenance of astroglial function is a beneficial response, rather than a disease-driving mechanism. Further studies are needed to explore the therapeutic potential of manipulating BuChE activity or astroglial functional status. (C) 2013 Elsevier Inc. All rights reserved.

  • 36.
    Denk, Stephanie
    et al.
    Univ Hosp Ulm, Germany.
    Neher, Miriam D.
    Univ Hosp Ulm, Germany.
    Messerer, David A. C.
    Univ Hosp Ulm, Germany.
    Wiegner, Rebecca
    Univ Hosp Ulm, Germany.
    Nilsson, Bo
    Uppsala University.
    Rittirsch, Daniel
    Univ Hosp Zurich, Switzerland.
    Nilsson Ekdahl, Kristina
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Weckbach, Sebastian
    Ulm Univ, Germany.
    Ignatius, Anita
    Ulm Univ, Germany.
    Kalbitz, Miriam
    Univ Hosp Ulm, Germany.
    Gebhard, Florian
    Univ Hosp Ulm, Germany.
    Weiss, Manfred E.
    Univ Hosp Ulm, Germany.
    Vogt, Josef
    Ulm Univ, Germany.
    Radermacher, Peter
    Ulm Univ, Germany.
    Koehl, Joerg
    Univ Lubeck, Germany ; Cincinnati Childrens Hosp Med Ctr, USA.
    Lambris, John D.
    Univ Penn, USA.
    Huber-Lang, Markus S.
    Univ Hosp Ulm, Germany.
    Complement C5a Functions as a Master Switch for the pH Balance in Neutrophils Exerting Fundamental Immunometabolic Effects2017In: Journal of Immunology, ISSN 0022-1767, E-ISSN 1550-6606, Vol. 198, no 12, p. 4846-4854Article in journal (Refereed)
    Abstract [en]

    During sepsis, excessive activation of the complement system with generation of the anaphylatoxin C5a results in profound disturbances in crucial neutrophil functions. Moreover, because neutrophil activity is highly dependent on intracellular pH (pH(i)), we propose a direct mechanistic link between complement activation and neutrophil pHi. In this article, we demonstrate that in vitro exposure of human neutrophils to C5a significantly increased pHi by selective activation of the sodium/hydrogen exchanger. Upstream signaling of C5a-mediated intracellular alkalinization was dependent on C5aR1, intracellular calcium, protein kinase C, and calmodulin, and downstream signaling regulated the release of antibacterial myeloperoxidase and lactoferrin. Notably, the pH shift caused by C5a increased the glucose uptake and activated glycolytic flux in neutrophils, resulting in a significant release of lactate. Furthermore, C5a induced acidification of the extracellular micromilieu. In experimental murine sepsis, pHi of blood neutrophils was analogously alkalinized, which could be normalized by C5aR1 inhibition. In the clinical setting of sepsis, neutrophils from patients with septic shock likewise exhibited a significantly increased pHi. These data suggest a novel role for the anaphylatoxin C5a as a master switch of the delicate pHi balance in neutrophils resulting in profound inflammatory and metabolic changes that contribute to hyperlactatemia during sepsis.

  • 37.
    Duehrkop, Claudia
    et al.
    Uppsala University.
    Leneweit, Gero
    ABNOBA GmbH, Germany ; Association for the Promotion of Cancer Therapy, Germany.
    Heyder, Christoph
    ABNOBA GmbH, Germany ; Association for the Promotion of Cancer Therapy, Germany.
    Fromell, Karin
    Uppsala University.
    Edwards, Katarina
    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.
    Development and characterization of an innovative heparin coating to stabilize and protect liposomes against adverse immune reactions2016In: Colloids and Surfaces B: Biointerfaces, ISSN 0927-7765, E-ISSN 1873-4367, Vol. 141, p. 576-583Article in journal (Refereed)
    Abstract [en]

    Liposomes have been recognized as excellent drug delivery systems, but when they come in direct contact with different blood components they may trigger an immediate activation of the innate immune system. The aim of the present study was to produce long-circulating, blood-compatible liposomes by developing a construct of liposomes covered by a novel unique heparin complex (CHC; 70 heparin molecules per complex) to avoid recognition by the innate immune system. Unilamellar, cationic liposomes were produced by hand extrusion through a 100-nm polycarbonate membrane. Coating of liposomes with the macromolecular CHC was accomplished by electrostatic interactions. Dynamic light scattering as well as QCM-D measurements were used to verify the electrostatic deposition of the negatively charged CHC to cationic liposomes. The CHC-coated liposomes did not aggregate when in contact with lepirudin anti coagulated plasma. Unlike previous attempts to coat liposomes with heparin, this technique produced freely moveable heparin strands sticking out from the liposome surface, which exposed AT binding sites reflecting the anticoagulant potentials of the liposomes. In experiments using lepirudin-anticoagulated plasma, CHC-coated liposomes, in contrast to non-coated control liposomes, did not activate the complement system, as evidenced by low C3a and sC5b-9 generation and reduced leakage from the liposomes. In conclusion, we show that liposomes can be successfully coated with the biopolymer CHC, resulting in biocompatible and stable liposomes that have significant application potential. (C) 2016 Elsevier B.V. All rights reserved.

  • 38.
    Ekstrand-Hammarström, Barbro
    et al.
    Swedish Def Res Agcy, Div CBRN Def & Secur, Linköping.
    Hong, Jaan
    Uppsala Univ.
    Davoodpour, Padideh
    Uppsala Univ.
    Sandholm, Kerstin
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Nilsson Ekdahl, Kristina
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences. Uppsala Univ.
    Bucht, Anders
    Umeå Univ.
    Nilsson, Bo
    Uppsala Univ.
    TiO2 nanoparticles tested in a novel screening whole human blood model of toxicity trigger adverse activation of the kallikrein system at low concentrations2015In: Biomaterials, ISSN 0142-9612, E-ISSN 1878-5905, Vol. 51, p. 58-68Article in journal (Refereed)
    Abstract [en]

    There is a compelling need to understand and assess the toxicity of industrially produced nanoparticles (NPs). In order to appreciate the long-term effects of NPs, sensitive human-based screening tests that comprehensively map the NP properties are needed to detect possible toxic mechanisms. Animal models can only be used in a limited number of test applications and are subject to ethical concerns, and the interpretation of experiments in animals is also distorted by the species differences. Here, we present a novel easy-to-perform highly sensitive whole-blood model using fresh non-anticoagulated human blood, which most justly reflects complex biological cross talks in a human system. As a demonstrator of the tests versatility, we evaluated the toxicity of TiO2 NPs that are widely used in various applications and otherwise considered to have relatively low toxic properties. We show that TiO2 NPs at very low concentrations (50 ng/mL) induce strong activation of the contact system, which in this model elicits thromboinflammation. These data are in line with the finding of components of the contact system in the protein corona of the TiO2 NPs after exposure to blood. The contact system activation may lead to both thrombotic reactions and generation of bradykinin, thereby representing fuel for chronic inflammation in vivo and potentially long-term risk of autoimmunity, arteriosclerosis and cancer. These results support the notion that this novel whole-blood model represents an important contribution to testing of NP toxicity. (C) 2015 Elsevier Ltd. All rights reserved.

  • 39.
    Engberg, Anna E.
    et al.
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences. Univ & Reg Labs, Dept Clin Chem, Region Skåne.
    Nilsson, Per H.
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences. Oslo Univ Hosp, Rikshosp, Dept Immunol, Oslo, Norway ; Univ Oslo, KG Jebsen ICR, N-0316 Oslo, Norway.
    Huang, Shan
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Fromell, Karin
    Uppsala Univ.
    Hamad, Osama A.
    Uppsala Univ.
    Mollnes, Tom Eirik
    Univ Oslo, Norway ; Univ Tromsö, Norway.
    Rosengren-Holmberg, Jenny P.
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences. Swedish Natl Lab Forens Sci, Linköping.
    Sandholm, Kerstin
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Teramura, Yuji
    Uppsala University ; Univ Tokyo, Japan.
    Nicholls, Ian A.
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences. Uppsala University.
    Nilsson, Bo
    Uppsala Univ.
    Nilsson Ekdahl, Kristina
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences. Uppsala Univ.
    Prediction of inflammatory responses induced by biomaterials in contact with human blood using protein fingerprint from plasma2015In: Biomaterials, ISSN 0142-9612, E-ISSN 1878-5905, Vol. 36, p. 55-65Article in journal (Refereed)
    Abstract [en]

    Inappropriate complement activation is often responsible for incompatibility reactions that occur when biomaterials are used. Complement activation is therefore a criterion included in legislation regarding biomaterials testing. However, no consensus is yet available regarding appropriate complement-activation-related test parameters. We examined protein adsorption in plasma and complement activation/cytokine release in whole blood incubated with well-characterized polymers. Strong correlations were found between the ratio of C4 to its inhibitor C4BP and generation of 10 (mainly pro-inflammatory) cytokines, including IL-17, IFN-gamma, and IL-6. The levels of complement activation products correlated weakly (C3a) or not at all (C5a, sC5b-9), confirming their poor predictive values. We have demonstrated a direct correlation between downstream biological effects and the proteins initially adhering to an artificial surface after contact with blood. Consequently, we propose the C4/C4BP ratio as a robust, predictor of biocompatibility with superior specificity and sensitivity over the current gold standard. (C) 2014 Elsevier Ltd. All rights reserved.

  • 40.
    Engberg, Anna E.
    et al.
    Linnaeus University, Faculty of Science and Engineering, School of Natural Sciences.
    Nilsson, Per H.
    Linnaeus University, Faculty of Science and Engineering, School of Natural Sciences.
    Mollnes, Tom Eirik
    Rosengren-Holmberg, Jenny P.
    Linnaeus University, Faculty of Science and Engineering, School of Natural Sciences.
    Nicholls, Ian A.
    Linnaeus University, Faculty of Science and Engineering, School of Natural Sciences.
    Nilsson, Bo
    Nilsson Ekdahl, Kristina
    Linnaeus University, Faculty of Science and Engineering, School of Natural Sciences.
    The ratio between C4 and C4BP adsorbed from plasma predicts cytokine generation induced by artificial polymers in contact with whole blood2012In: Immunobiology, ISSN 0171-2985, E-ISSN 1878-3279, Vol. 217, no 11, p. 1211-1211Article in journal (Other academic)
  • 41.
    Engberg, Anna E.
    et al.
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Nilsson, Per H.
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences. Univ Oslo, Rikshosp, Univ Hosp, Inst Immunol, N-0027 Oslo, Norway.
    Sandholm, Kerstin
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Huang, Shan
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Mollnes, T. E.
    Nicholls, Ian A.
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences. Uppsala Univ, Dept Chem, Uppsala, Sweden.
    Nilsson, B.
    Nilsson Ekdahl, Kristina
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences. Rudbeck Lab C5 3, Dept Immunol Genet & Pathol IGP, Rudbeck, Sweden.
    The ratio between C4 and C4BP adsorbed to artificial materials is a new predictor for biocompatibility2013In: Molecular Immunology, ISSN 0161-5890, E-ISSN 1872-9142, Vol. 56, no 3, p. 309-309Article in journal (Other academic)
  • 42.
    Engberg, Anna E.
    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.
    Nicholls, Ian A.
    University of Kalmar, School of Pure and Applied Natural Sciences.
    Nilsson Ekdahl, Kristina
    University of Kalmar, School of Pure and Applied Natural Sciences.
    Development of novel biomaterial surfaces and evaluation of their hemocompatibility*2008In: Journal of Molecular Immunology 45, 2008Conference paper (Refereed)
  • 43.
    Engberg, Anna E.
    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.
    Nicholls, Ian A.
    University of Kalmar, School of Pure and Applied Natural Sciences.
    Nilsson Ekdahl, Kristina
    University of Kalmar, School of Pure and Applied Natural Sciences.
    Development of novel biomaterial surfaces and evaluation of their hemocompatibility2008Conference paper (Refereed)
  • 44.
    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 Ekdahl, Kristina
    University of Kalmar, School of Pure and Applied Natural Sciences.
    Nicholls, Ian A.
    University of Kalmar, School of Pure and Applied Natural Sciences.
    Synthesis of new polymers and evaluation of their hemocompatibility2009Conference paper (Refereed)
  • 45.
    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

  • 46.
    Engberg, Anna E.
    et al.
    University of Kalmar, School of Pure and Applied Natural Sciences.
    Sandholm, Kerstin
    University of Kalmar, School of Pure and Applied Natural Sciences.
    Bexborn, Fredrik
    University of Kalmar, School of Pure and Applied Natural Sciences.
    Persson, Jenny
    Lund University.
    Nilsson, Bo
    Uppsala University.
    Lindahl, Gunnar
    Lund University.
    Nilsson Ekdahl, Kristina
    University of Kalmar, School of Pure and Applied Natural Sciences. Uppsala University.
    Inhibition of complement activation on a model biomaterial surface by streptococcal M protein-derived peptides2009In: Biomaterials, ISSN 0142-9612, E-ISSN 1878-5905, Vol. 30, no 13, p. 2653-2659Article in journal (Refereed)
    Abstract [en]

    The aim of this study was to evaluate a new approach to inhibit complement activation triggered by biomaterial surfaces in contact with blood. In order to inhibit complement activation initiated by the classical pathway (CP), we used streptococcal M protein-derived peptides that specifically bind human C4BP, an inhibitor of the CP. The peptides were used to coat polystyrene microtiter wells which served as a model biomaterial. The ability of coated peptides to bind C4BP and to attenuate complement activation via the CP (monitored as generation of fluid-phase C3a and binding of fragments of C3 and C4 to the surface) was investigated using diluted normal human serum, where complement activation by the AP is minimal, as well as serum from a patient lacking alternative pathway activation. Complement activation (all parameters) was significantly decreased in serum incubated in well surfaces coated with peptides. Total inhibition of complement activation was obtained at peptide coating concentrations as low as 1-5 mu g/mL. Successful use of Streptococcus-derived peptides shows that it is feasible to control complement activation at a model biomaterial surface by capturing autologous complement regulatory molecules from plasma. (C) 2009 Elsevier Ltd. All rights reserved.

  • 47.
    Forsberg, Ulf
    et al.
    Umeå universitet.
    Jonsson, Per
    Umeå universitet.
    Stegmayr, Christofer
    Umeå universitet.
    Jonsson, Fredrik
    Umeå universitet.
    Nilsson, Bo
    Uppsala universitet.
    Nilsson Ekdahl, Kristina
    Uppsala universitet.
    Stegmayr, Bernd
    Umeå universitet.
    A high blood level in the venous chamber and a wet-stored dialyzer help to reduce exposure for microemboli during hemodialysis2013In: Hemodialysis International, ISSN 1492-7535, E-ISSN 1542-4758, Vol. 17, no 4, p. 612-617Article in journal (Refereed)
    Abstract [en]

    During hemodialysis (HD), microemboli develop in the blood circuit of the apparatus. These microemboli can pass through the venous chamber and enter into the patient's circulation. The aim of this study was to investigate whether it is possible to reduce the risk for exposure of microemboli by altering of the treatment mode. Twenty patients on chronic HD were randomized to a prospective cross-over study of three modes of HD: (a) a dry-stored dialyzer (F8HPS, Fresenius, steam sterilized) with a low blood level in the venous chamber (DL), (b) the same dialyzer as above, but with a high level in the venous chamber (DH), and (c) a wet-stored dialyzer (Rexeed, Asahi Kasei Medical, gamma sterilized) with a high blood level (WH). Microemboli measurements were obtained in a continuous fashion during 180 minutes of HD for all settings. A greater number of microemboli were detected during dialysis with the setting DL vs. WH (odds ratio [OR] 4.07, 95% confidence interval [CI] 4.03-4.11, P<0.0001) and DH vs. WH (OR 1.18, 95% CI 1.17-1.19, P<0.0001) and less for DH vs. DL (OR 0.290, 95% CI 0.288-0.2930.288-0.293, P<0.0001). These data indicate that emboli exposure was least when using WH, greater with DH, and most with DL. This study shows that using a high blood level in the venous chamber and wet-stored dialyzers may reduce the number of microemboli.

    CallSend SMSAdd to SkypeYou'll need Skype CreditFree via Skype

  • 48.
    Fromell, Karin
    et al.
    Uppsala University.
    Duhrkop, Claudia
    Uppsala University.
    Johansson, Ulrika
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Nilsson Ekdahl, Kristina
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences. Uppsala University.
    Nilsson, Bo
    Uppsala University.
    Forms of contact-activated C3 associated with AP convertase formation2017In: Molecular Immunology, ISSN 0161-5890, E-ISSN 1872-9142, Vol. 89, p. 141-141Article in journal (Other academic)
  • 49.
    Fromell, Karin
    et al.
    Uppsala University.
    Yang, Yi
    Gothenburg University.
    Nilsson Ekdahl, Kristina
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences. Uppsala University.
    Nilsson, Bo
    Uppsala University.
    Berglin, Mattias
    Gothenburg University ; RISE Res Inst Sweden Chem Mat & Surfaces.
    Elwing, Hans
    Gothenburg University.
    Absence of conformational change in complement factor 3 and factor XII adsorbed to acrylate polymers is related to a high degree of polymer backbone flexibility2017In: Biointerphases, ISSN 1934-8630, E-ISSN 1559-4106, Vol. 12, no 2, article id 02D417Article in journal (Refereed)
    Abstract [en]

    In previous investigations, the authors have examined the adsorption of albumin, immunoglobulin, and fibrinogen to a series of acrylate polymers with different backbone and side-group flexibility. The authors showed that protein adsorption to acrylates with high flexibility, such as poly(lauryl methacrylate) (PLMA), tends to preserve native conformation. In the present study, the authors have continued this work by examining the conformational changes that occur during the binding of complement factor 3 (C3) and coagulation factor XII (FXII). Native C3 adsorbed readily to all solid surfaces tested, including a series of acrylate surfaces of varying backbone flexibility. However, a monoclonal antibody recognizing a "hidden" epitope of C3 (only exposed during C3 activation or denaturation) bound to the C3 on the rigid acrylate surfaces or on polystyrene (also rigid), but not to C3 on the flexible PLMA, indicating that varying degrees of conformational change had occurred with binding to different surfaces. Similarly, FXII was activated only on the rigid poly(butyl methacrylate) surface, as assessed by the formation of FXIIa-antithrombin (AT) complexes; in contrast, it remained in its native form on the flexible PLMA surface. The authors also found that water wettability hysteresis, defined as the difference between the advancing and receding contact angles, was highest for the PLMA surface, indicating that a dynamic change in the interface polymer structure may help protect the adsorbed protein from conformational changes and denaturation. (C) 2017 Author(s).

  • 50. Gong, J
    et al.
    Larsson, R
    Nilsson Ekdahl, Kristina
    University of Kalmar, School of Pure and Applied Natural Sciences.
    Mollnes, T E
    Nilsson, U R
    Nilsson, B
    Chandler loops as a model for cardiopulmonary bypass circuits: Both the biomaterial and the blood- gas interaces induce complement activation in an in vitro model1996In: Journal of clinical immunology, Vol. 16, p. 223-230Article in journal (Refereed)
12345 1 - 50 of 204
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