Contribution of chondroitin sulfate A to the binding of complement proteins to activated platelets

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Hamad, Osama A.,1978-Uppsala universitet,Enheten för klinisk immunologi,Complement And Biomaterials,Uppsala University (author)

Contribution of chondroitin sulfate A to the binding of complement proteins to activated platelets

Article/chapterEnglish2010

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2010-09-23
Public Library of Science (PLoS),2010
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LIBRIS-ID:oai:DiVA.org:uu-123614
https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-123614URI
https://doi.org/10.1371/journal.pone.0012889DOI
https://urn.kb.se/resolve?urn=urn:nbn:se:lnu:diva-7683URI

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Language:English
Summary in:English

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Exposure of chondroitin sulfate A (CS-A) on the surface of activated platelets is well established. The aim of the present study was to investigate to what extent CS-A contributes to the binding of C1q and the complement regulators C1 inhibitor (C1INH), C4b-binding protein (C4BP), and factor H to platelets. Human serum was passed over Sepharose conjugated with CS-A, and bound proteins were identified by Western blotting, and mass spectrometric analysis. C1q was identified as the main protein that specifically bound to CS-A, but C4BP and factor H were also shown to interact. Binding of C1INH was dependent of the presence of C1q and not bound to CS-A from C1q-depleted serum. The specific interactions observed of these proteins with CS-A were subsequently confirmed by surface plasmon resonance analysis using purified proteins. Importantly, C1q, C4BP, and factor H were shown to bind also to activated platelets and this interaction was inhibited by a CS-A-specific monoclonal antibody, thereby linking the binding of C1q, C4BP, and factor H to exposure of CS-A on platelets. CS-A-bound C1q was also shown to amplify the binding of model immune complexes to both microtiter plate-bound CS-A and to activated platelets. In conclusion, this study supports the concept that CS-A contributes to the binding of C1q, C4BP, and factor H to platelets, thereby adding CS-A to the previously reported binding sites for these proteins on the platelet surface. CS-A-bound C1q seems to amplify the binding of immune complexes to activated platelets, suggesting a role for this molecule in immune complex diseases.

Subject headings and genre

MEDICIN OCH HÄLSOVETENSKAP Medicinska och farmaceutiska grundvetenskaper Immunologi inom det medicinska området hsv//swe
MEDICAL AND HEALTH SCIENCES Basic Medicine Immunology in the medical area hsv//eng
MEDICIN OCH HÄLSOVETENSKAP Medicinsk bioteknologi Biomedicinsk laboratorievetenskap/teknologi hsv//swe
MEDICAL AND HEALTH SCIENCES Medical Biotechnology Biomedical Laboratory Science/Technology hsv//eng
chondroitin sulfate
activated platelets
complement proteins
complement inhibitors
TRAP
C1q
Immunology
Immunologi
Klinisk immunologi
Clinical Immunology
MEDICINE
Biomedical Sciences

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Nilsson Ekdahl, KristinaLinnéuniversitetet,Institutionen för naturvetenskap, NV,Uppsala University(Swepub:lnu)nnikr (author)
Nilsson, Per H.Linnéuniversitetet,Institutionen för naturvetenskap, NV(Swepub:lnu)enipe (author)
Lasaosa, MariaUniversity of Pennsylvania, USA (author)
Ricklin, DanielUniversity of Pennsylvania, USA (author)
Lambris, John D.University of Pennsylvania, USA (author)
Nilsson, BoUppsala University (author)
Uppsala universitetEnheten för klinisk immunologi (creator_code:org_t)

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In:PLoS ONE: Public Library of Science (PLoS)5:9, s. e12889-1932-6203

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MEDICAL AND HEALTH SCIENCES: MEDICAL AND HEAL ...; and Basic Medicine; and Immunology in th ...

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