Contribution of chondroitin sulfate A to the binding of complement proteins to activated platelets
2010 (English)In: PLoS ONE, ISSN 1932-6203, Vol. 5, no 9, e12889- p.Article in journal (Refereed) Published
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.
Place, publisher, year, edition, pages
2010. Vol. 5, no 9, e12889- p.
chondroitin sulfate, activated platelets, complement proteins, complement inhibitors, TRAP, C1q
Immunology in the medical area
Research subject Clinical Immunology
IdentifiersURN: urn:nbn:se:uu:diva-123614DOI: 10.1371/journal.pone.0012889ISI: 000282091100006OAI: oai:DiVA.org:uu-123614DiVA: diva2:315100
Projectsplatelet mediated complement activation