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Nilsson Ekdahl, KristinaORCID iD iconorcid.org/0000-0001-7888-1571
Publications (10 of 208) Show all publications
Mohlin, C., Sandholm, K., Kvanta, A., Nilsson Ekdahl, K. & Johansson, K. (2018). A model to study complement involvement in experimental retinal degeneration.. Upsala Journal of Medical Sciences, 123(1), 28-42
Open this publication in new window or tab >>A model to study complement involvement in experimental retinal degeneration.
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2018 (English)In: Upsala Journal of Medical Sciences, ISSN 0300-9734, E-ISSN 2000-1967, Vol. 123, no 1, p. 28-42Article in journal (Refereed) Published
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.

Place, publisher, year, edition, pages
Taylor & Francis, 2018
Keywords
AMD, RPE, complement system, ocular diseases, retina
National Category
Immunology in the medical area
Research subject
Biomedical Sciences, Immunology
Identifiers
urn:nbn:se:lnu:diva-71489 (URN)10.1080/03009734.2018.1431744 (DOI)000428060300004 ()29436895 (PubMedID)
Available from: 2018-03-12 Created: 2018-03-12 Last updated: 2018-04-19Bibliographically approved
Huber-Lang, M., Nilsson Ekdahl, K., Wiegner, R., Fromell, K. & Nilsson, B. (2018). Auxiliary activation of the complement system and its importance for the pathophysiology of clinical conditions. Seminars in Immunopathology, 40(1), 87-102
Open this publication in new window or tab >>Auxiliary activation of the complement system and its importance for the pathophysiology of clinical conditions
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2018 (English)In: Seminars in Immunopathology, ISSN 1863-2297, E-ISSN 1863-2300, Vol. 40, no 1, p. 87-102Article, review/survey (Refereed) Published
Abstract [en]

Activation and regulation of the cascade systems of the blood (the complement system, the coagulation/contact activation/kallikrein system, and the fibrinolytic system) occurs via activation of zymogen molecules to specific active proteolytic enzymes. Despite the fact that the generated proteases are all present together in the blood, under physiological conditions, the activity of the generated proteases is controlled by endogenous protease inhibitors. Consequently, there is remarkable little crosstalk between the different systems in the fluid phase. This concept review article aims at identifying and describing conditions where the strict system-related control is circumvented. These include clinical settings where massive amounts of proteolytic enzymes are released from tissues, e.g., during pancreatitis or post-traumatic tissue damage, resulting in consumption of the natural substrates of the specific proteases and the available protease inhibitor. Another example of cascade system dysregulation is disseminated intravascular coagulation, with canonical activation of all cascade systems of the blood, also leading to specific substrate and protease inhibitor elimination. The present review explains basic concepts in protease biochemistry of importance to understand clinical conditions with extensive protease activation.

Place, publisher, year, edition, pages
Springer, 2018
Keywords
Complement system, Proteases, Protease inhibitors, Trauma
National Category
Immunology
Research subject
Biomedical Sciences, Immunology
Identifiers
urn:nbn:se:lnu:diva-70933 (URN)10.1007/s00281-017-0646-9 (DOI)000424058800008 ()28900700 (PubMedID)
Available from: 2018-02-15 Created: 2018-02-15 Last updated: 2018-02-15Bibliographically approved
Nilsson Ekdahl, K., Davoodpour, P., Ekstrand-Hammarström, B., Fromell, K., Hamad, O. A., Hong, J., . . . Nilsson, B. (2018). Contact (kallikrein/kinin) system activation in whole human blood induced by low concentrations of α-Fe2O3 nanoparticles. Nanomedicine: Nanotechnology, Biology and Medicine, 14(3), 735-744
Open this publication in new window or tab >>Contact (kallikrein/kinin) system activation in whole human blood induced by low concentrations of α-Fe2O3 nanoparticles
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2018 (English)In: Nanomedicine: Nanotechnology, Biology and Medicine, ISSN 1549-9634, E-ISSN 1549-9642, Vol. 14, no 3, p. 735-744Article in journal (Refereed) Published
Abstract [en]

Iron-oxide nanoparticles (NPs) generated by environmental events are likely to represent health problems. α-Fe2O3 NPs were synthesized, characterized and tested in a model for toxicity utilizing human whole blood without added anticoagulant. MALDI-TOF of the corona was performed and activation markers for plasma cascade systems (complement, contact and coagulation systems), platelet consumption and release of growth factors, MPO, and chemokine/cytokines from blood cells were analyzed. The coronas formed on the pristine α-Fe2O3 NPs contained contact system proteins and they induced massive activation of the contact (kinin/kallikrein) system, as well as thrombin generation, platelet activation, and release of two pro-angiogeneic growth factors: platelet-derived growth factor and vascular endothelial growth factor, whereas complement activation was unaffected. The α-Fe2O3 NPs exhibited a noticeable toxicity, with kinin/kallikreinactivation, which may be associated with hypotension and long-term angiogenesis in vivo, with implications for cancer, arteriosclerosis and pulmonary disease.

Place, publisher, year, edition, pages
Elsevier, 2018
Keywords
Contact/kallikrein system, Innate immunity, α-Fe(2)O(3) NPs
National Category
Immunology
Research subject
Biomedical Sciences, Immunology
Identifiers
urn:nbn:se:lnu:diva-73041 (URN)10.1016/j.nano.2017.12.008 (DOI)000429528900010 ()29277639 (PubMedID)
Available from: 2018-04-19 Created: 2018-04-19 Last updated: 2018-07-10Bibliographically approved
Labriere, C., Kondori, N., Caous, J. S., Boomgaren, M., Sandholm, K., Nilsson Ekdahl, K., . . . Svenson, J. (2018). Development and evaluation of cationic amphiphilic antimicrobial 2,5-diketopiperazines. Paper presented at 7th International Meeting on Antimicrobial Peptides, AUG 25-27, 2017, Univ Copenhagen, Copenhagen, DENMARK. Journal of Peptide Science, 24(7), Article ID UNSP e3090.
Open this publication in new window or tab >>Development and evaluation of cationic amphiphilic antimicrobial 2,5-diketopiperazines
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2018 (English)In: Journal of Peptide Science, ISSN 1075-2617, E-ISSN 1099-1387, Vol. 24, no 7, article id UNSP e3090Article in journal (Refereed) Published
Abstract [en]

Both pathogenic bacteria and fungi are developing resistance to common antimicrobial treatment at an alarming rate. To counteract this development, it is of essence to develop new classes of antimicrobial agents. One such class is antimicrobial peptides, most of which are derived from the innate immune system. In this study, a series of novel 2,5-diketopiperazines were designed, synthesized, and evaluated for their antimicrobial abilities. The compounds were designed to probe the pharmacophore dictated for short linear mimics of antimicrobial cationic peptides, and as such, the compounds contain a range of cationic and hydrophobic functionalities. Several of the prepared compounds displayed high antimicrobial activities toward bacteria and also against human pathogenic fungi. Of particular interest was the high activity toward fungal strains with an inherent increased resistance toward conventional antifungal agents. The most effective compounds displayed inhibition of Candida glabrata and Candida krusei growth at concentrations between 4 and 8 mu g/mL, which is comparable to commercial antifungal agents in use. Structure activity relationship studies revealed a similar dependence on cationic charge and the volume of the hydrophobic bulk as for linear cationic antimicrobial peptides. Finally, the hemolytic activity of selected compounds was evaluated, which revealed a potential to produce active compounds with attenuation of unwanted hemolysis. The findings highlight the potential of cyclic cationic amphiphilic peptidomimetics as a class of promising compounds for the treatment of infections caused by microorganisms with an increased resistance to conventional antimicrobial agents.

Place, publisher, year, edition, pages
John Wiley & Sons, 2018
Keywords
2, 5-diketopiperazine, antifungal agents, antimicrobial, Candida krusei, MRSA, structure-activity relationship
National Category
Biochemistry and Molecular Biology
Research subject
Natural Science, Biomedical Sciences
Identifiers
urn:nbn:se:lnu:diva-77499 (URN)10.1002/psc.3090 (DOI)000440144700005 ()29845683 (PubMedID)
Conference
7th International Meeting on Antimicrobial Peptides, AUG 25-27, 2017, Univ Copenhagen, Copenhagen, DENMARK
Available from: 2018-08-31 Created: 2018-08-31 Last updated: 2018-08-31Bibliographically approved
Fromell, K., Johansson, U., Duhrkop, C., Adler, A., Usterud, E., Hamad, O. A., . . . Nilsson, B. (2018). Generation of an alternative pathway convertase by contact-activated C3 is dependent on the conformation of C3. Paper presented at 27th International Complement Workshop (ICW), SEP 16-20, 2018, Santa Fe, NM. Molecular Immunology, 102, 193-193
Open this publication in new window or tab >>Generation of an alternative pathway convertase by contact-activated C3 is dependent on the conformation of C3
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2018 (English)In: Molecular Immunology, ISSN 0161-5890, E-ISSN 1872-9142, Vol. 102, p. 193-193Article in journal, Meeting abstract (Other academic) Published
Place, publisher, year, edition, pages
Elsevier, 2018
Keywords
Complement C3
National Category
Immunology
Research subject
Biomedical Sciences, Immunology
Identifiers
urn:nbn:se:lnu:diva-78410 (URN)10.1016/j.molimm.2018.06.167 (DOI)000445313600163 ()
Conference
27th International Complement Workshop (ICW), SEP 16-20, 2018, Santa Fe, NM
Available from: 2018-10-22 Created: 2018-10-22 Last updated: 2018-10-22Bibliographically approved
Mohlin, C., Petrus-Reurer, S., Lanner, F., Sandholm, K., Nilsson, P. H., Nilsson, B. & Nilsson Ekdahl, K. (2018). Is the polarized secretion of complement factor H of importance in age-related macular degeneration?. Paper presented at Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology (ARVO), APR 29-MAY 03, 2018, Honolulu, HI. Investigative Ophthalmology and Visual Science, 59(9)
Open this publication in new window or tab >>Is the polarized secretion of complement factor H of importance in age-related macular degeneration?
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2018 (English)In: Investigative Ophthalmology and Visual Science, ISSN 0146-0404, E-ISSN 1552-5783, Vol. 59, no 9Article in journal, Meeting abstract (Other academic) Published
Place, publisher, year, edition, pages
ASSOC RESEARCH VISION OPHTHALMOLOGY INC, 2018
National Category
Ophthalmology
Research subject
Natural Science, Optometry
Identifiers
urn:nbn:se:lnu:diva-78425 (URN)000442932806149 ()
Conference
Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology (ARVO), APR 29-MAY 03, 2018, Honolulu, HI
Available from: 2018-10-22 Created: 2018-10-22 Last updated: 2018-10-22Bibliographically approved
van Griensven, M., Ricklin, D., Denk, S., Halbgebauer, R., Braun, C. K., Schultze, A., . . . Huber-Lang, M. (2018). Protective Effects of the Complement Inhibitor Compstatin CP40 in Hemorrhagic Shock. Shock, February 14
Open this publication in new window or tab >>Protective Effects of the Complement Inhibitor Compstatin CP40 in Hemorrhagic Shock
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2018 (English)In: Shock, ISSN 1073-2322, E-ISSN 1540-0514, Vol. February 14Article in journal (Refereed) Epub ahead of print
Abstract [en]

Trauma-induced hemorrhagic shock (HS) plays a decisive role in the development of immune, coagulation, and organ dysfunction often resulting in a poor clinical outcome. Imbalanced complement activation is intricately associated with the molecular danger response and organ damage after HS. Thus, inhibition of the central complement component C3 as turnstile of both inflammation and coagulation is hypothesized as a rational strategy to improve the clinical course after HS.Applying intensive care conditions, anaesthetized, monitored, and protectively ventilated non-human primates (NHP; cynomolgus monkeys) received a pressure-controlled severe HS (60 min at MAP 30 mmHg) with subsequent volume resuscitation. Thirty min after HS, animals were randomly treated with either an analog of the C3 inhibitor compstatin (i.e., Cp40) in saline (n = 4) or with saline alone (n = 4). The observation period lasted 300 min after induction of HS.We observed improved kidney function in compstatin Cp40-treated animals after HS as determined by improved urine output, reduced damage markers and a tendency of less histopathological signs of acute kidney injury. Sham-treated animals revealed classical signs of mucosal edema, especially in the ileum and colon reflected by worsened microscopic intestinal injury scores. In contrast, Cp40-treated HS animals exhibited only minor signs of organ edema and significantly less intestinal damage. Furthermore, early systemic inflammation and coagulation dysfunction were both ameliorated by Cp40.The data suggest that therapeutic inhibition of C3 is capable to significantly improve immune, coagulation and organ function and to preserve organ-barrier integrity early after traumatic HS. C3-targeted complement inhibition may therefore reflect a promising therapeutic strategy in fighting fatal consequences of HS.

National Category
Immunology
Research subject
Biomedical Sciences, Immunology
Identifiers
urn:nbn:se:lnu:diva-73044 (URN)10.1097/SHK.0000000000001127 (DOI)29461464 (PubMedID)
Available from: 2018-04-19 Created: 2018-04-19 Last updated: 2018-05-11
Fromell, K., Duhrkop, C., Kozarcanin, H., Johansson, U., Skjoedt, M.-O., Garred, P., . . . Nilsson, B. (2018). The lectin pathway of complement and the contact/kallikrein system are integrated. Paper presented at 27th International Complement Workshop (ICW), SEP 16-20, 2018, Santa Fe, NM. Molecular Immunology, 102, 151-152
Open this publication in new window or tab >>The lectin pathway of complement and the contact/kallikrein system are integrated
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2018 (English)In: Molecular Immunology, ISSN 0161-5890, E-ISSN 1872-9142, Vol. 102, p. 151-152Article in journal, Meeting abstract (Other academic) Published
Place, publisher, year, edition, pages
Elsevier, 2018
Keywords
Lectin pathway, Contact system, Clotting, Fibrin
National Category
Immunology
Research subject
Biomedical Sciences, Immunology
Identifiers
urn:nbn:se:lnu:diva-78409 (URN)10.1016/j.molimm.2018.06.071 (DOI)000445313600067 ()
Conference
27th International Complement Workshop (ICW), SEP 16-20, 2018, Santa Fe, NM
Available from: 2018-10-22 Created: 2018-10-22 Last updated: 2018-10-22Bibliographically approved
Nilsson, B., Asif, S., Nilsson Ekdahl, K., Manell, E., Biglarnia, A., Jensen-Waern, M. & Teramura, Y. (2017). A protective role of complement regulators linked to a PEG phospholipid construct in reducing ischemic reperfusion injury in transplantation. Paper presented at 16th European Meeting on Complement in Human Disease (EMCHD), SEP 08-12, 2017, Copenhagen, DENMARK. Molecular Immunology, 89, 208-208
Open this publication in new window or tab >>A protective role of complement regulators linked to a PEG phospholipid construct in reducing ischemic reperfusion injury in transplantation
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2017 (English)In: Molecular Immunology, ISSN 0161-5890, E-ISSN 1872-9142, Vol. 89, p. 208-208Article in journal, Meeting abstract (Other academic) Published
National Category
Immunology
Research subject
Biomedical Sciences, Immunology
Identifiers
urn:nbn:se:lnu:diva-68149 (URN)10.1016/j.molimm.2017.06.214 (DOI)000410014500195 ()
Conference
16th European Meeting on Complement in Human Disease (EMCHD), SEP 08-12, 2017, Copenhagen, DENMARK
Available from: 2017-10-02 Created: 2017-10-02 Last updated: 2018-01-10Bibliographically approved
Fromell, K., Yang, Y., Nilsson Ekdahl, K., Nilsson, B., Berglin, M. & Elwing, H. (2017). Absence of conformational change in complement factor 3 and factor XII adsorbed to acrylate polymers is related to a high degree of polymer backbone flexibility. Biointerphases, 12(2), Article ID 02D417.
Open this publication in new window or tab >>Absence of conformational change in complement factor 3 and factor XII adsorbed to acrylate polymers is related to a high degree of polymer backbone flexibility
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2017 (English)In: Biointerphases, ISSN 1934-8630, E-ISSN 1559-4106, Vol. 12, no 2, article id 02D417Article in journal (Refereed) Published
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).

National Category
Biophysics
Research subject
Natural Science, Biomedical Sciences
Identifiers
urn:nbn:se:lnu:diva-66908 (URN)10.1116/1.4985698 (DOI)000404045100001 ()
Available from: 2017-07-13 Created: 2017-07-13 Last updated: 2018-08-30Bibliographically approved
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Identifiers
ORCID iD: ORCID iD iconorcid.org/0000-0001-7888-1571

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