C1Q AUGMENTS PLATELET ACTIVATION IN RESPONSE TO AGGREGATED IG

Immune complexes and aggregated IgG (agg-IgG) induce platelet aggregat ion and the release reaction, Immune complexes also activate the compl ement system and interact with the complement component C1q. Since pla telets possess both Fe and C1q receptors capable of signal transductio n, the present study focused on the interaction between these binding sites and platelet activation, Subaggregating doses of agg-IgG (20-400 mu g/ml) were identified for washed platelets from each of la healthy donors, and platelet aggregation was monitored in the presence or the absence of increasing concentrations of C1q (5-100 mu g/ml) C1q produ ced a dose-dependent potentiation of platelet alpha(IIb)/beta(3) integ rin activation, platelet aggregation, and granule secretion when combi ned with low doses of agg-IgG, C1q alone was without effect, Maximal e nhancement of agg-IgG-induced platelet activation was noted at C1q con centrations ranging from 50 to 100 mu g/ml, The observed C1q-induced p otentiation of platelet aggregation in response to agg-IgG was blocked by polyclonal antibody F(ab')(2) directed against platelet binding si tes recognizing the collagen-like domain of C1q (cC1qR) or by mAb Fab (IV.3) directed against platelet Fc gamma RII receptors, These data su ggest a cooperative interaction between platelet Fc gamma RII and cC1q receptors and support a potential role for platelet cC1q receptors in pathologic platelet activation by circulating immune complexes often associated with in viva thrombosis and thrombocytopenia.