Non-proteolytically activated C3 promotes binding of activated platelets and platelet-derived microparticles to leukocytes via CD11b/CD18
2012 (English)In: Immunobiology, ISSN 0171-2985, E-ISSN 1878-3279, Vol. 217, no 11, 1191-1191 p.Article in journal, Meeting abstract (Refereed) Published
We have previously demonstrated that complement component C3 binds to the surface of activated platelets, independent of proteolytic activation. The resulting form of C3, termed C3(H2O), was shown to be a ligand for recombinant CD35 (complement receptor 1, CR1). Previous studies by others have indicated that platelet-leukocyte complex (PLC) formation is dependent on the interaction between platelet exposed P-selectin (CD62P) and its ligand, PSGL-1, on leukocytes. In addition, CD11b/CD18 (Mac-1 or CR3) has been shown to participate in this reaction, but its ligand has not yet been identified.
To test the hypothesis that C3 bound to activated platelets and platelet-derived microparticles (PMPs) can act as a ligand for CD11b/CD18 (CR3) and contribute to PLC formation.
Methods and results:
Blood cells were depleted of plasma proteins. After extensive washing, C3 was added, and the leukocytes were activated with C5a and the platelets with thrombin receptor-activating peptide (TRAP). PLC formation was detected by flow cytometry (monocytes: CD14+/CD42a+, granulocytes: CD16+/CD42a+). For both granulocytes and monocytes, the addition of C3 significantly enhanced PLC formation. Formation of PLC was inhibited by both anti-P-selectin and anti-CD11b monoclonal antibodies. In addition, PMPs isolated from serum, were found to expose C3(H2O) and bind to leukocytes in a fashion similar to activated platelets.
We have identified proteolytically non-activated C3 as a ligand for CD11b in the formation of PLC and possibly the binding of PMPs to leukocytes. This observation most likely has pathophysiological implications for the recently reported links between thrombotic disease and the complement system.
Place, publisher, year, edition, pages
2012. Vol. 217, no 11, 1191-1191 p.
platelet activation, complement, platelet-leukocyte complexes, PMP, CD11b/CD18, complement component 3
Immunology in the medical area
Research subject Clinical Immunology
IdentifiersURN: urn:nbn:se:uu:diva-123624DOI: 10.1016/j.imbio.2012.08.178ISI: 000311187800190OAI: oai:DiVA.org:uu-123624DiVA: diva2:315111
Aegean Conferences, XXIV International Complement Workshop, 10-15 October, 2012, Chania, Crete, GREECE
Projectsplatelet mediated complement activation