C1q augments platelet activation in response to aggregated Ig.
Immune complexes and aggregated IgG (agg-IgG) induce platelet aggregation and the release reaction. Immune complexes also activate the complement system and interact with the complement component C1q. Since platelets possess both Fc and C1q receptors capable of signal transduction, the present study focused on the interaction between these binding sites and platelet activation. Subaggregating doses of agg-IgG (20-400 microg/ml) were identified for washed platelets from each of 11 healthy donors, and platelet aggregation was monitored in the presence or the absence of increasing concentrations of C1q (5-100 microg/ml). C1q produced a dose-dependent potentiation of platelet alphaIIb/beta3 integrin activation, platelet aggregation, and granule secretion when combined with low doses of agg-IgG. C1q alone was without effect. Maximal enhancement of agg-IgG-induced platelet activation was noted at C1q concentrations ranging from 50 to 100 microg/ml. The observed C1q-induced potentiation of platelet aggregation in response to agg-IgG was blocked by polyclonal antibody F(ab')2 directed against platelet binding sites recognizing the collagen-like domain of C1q (cC1qR) or by mAb Fab (IV.3) directed against platelet FcgammaRII receptors. These data suggest a cooperative interaction between platelet FcgammaRII and cC1q receptors and support a potential role for platelet cC1q receptors in pathologic platelet activation by circulating immune complexes often associated with in vivo thrombosis and thrombocytopenia.
Peerschke
E I
EI
Department of Pathology, State University of New York, Stony Brook 11790, USA.
Ghebrehiwet
B
B
D000911:Antibodies, Monoclonal / Q000494:pharmacology; D015922:Complement C1q / Q000008:administration & dosage / Q000494:pharmacology*; D006358:Hot Temperature; D006801:Humans; D007074:Immunoglobulin G / Q000008:administration & dosage / Q000494:pharmacology*; D010766:Phosphorylation; D015539:Platelet Activation; D011494:Protein Kinases / Q000378:metabolism; D017452:Receptors, IgG / Q000276:immunology; D011971:Receptors, Immunologic / Q000276:immunology
D000911:Antibodies, Monoclonal; C052643:F(ab')2 receptor; D007074:Immunoglobulin G; D017452:Receptors, IgG; D011971:Receptors, Immunologic; D015922:Complement C1q; D011494:Protein Kinases