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. 1993 Aug 1;178(2):579–587. doi: 10.1084/jem.178.2.579

Platelet activation by C1q results in the induction of alpha IIb/beta 3 integrins (GPIIb-IIIa) and the expression of P-selectin and procoagulant activity

PMCID: PMC2191135  PMID: 7688027

Abstract

C1q receptors (C1qR) have been identified on a variety of somatic and cultured cells including peripheral blood platelets. Since platelets are likely to encounter both circulating C1q multimers and C1q associated with the extracellular matrix after complement activation by the classical pathway, the present study was designed to assess the effect of fluid phase and immobilized C1q on platelet function. Platelet adhesion to C1q-coated surfaces was accompanied by the induction of fibrinogen receptors. Scatchard analysis of fibrinogen binding to adherent platelets revealed the binding of approximately 10,000 molecules of fibrinogen per platelet with a Kd of 0.1 +/- 0.03 microM (mean +/- SD, n = 4). Furthermore, fluid phase C1q multimers were noted to aggregate platelets at doses > 5 micrograms/ml. This aggregation was preceded by a rise in inositol-1,4,5-trisphosphate (IP3) (6.9 +/- 2.4 pmoles/10(9) platelets at 15 s, n = 4), and activation of GPIIb-IIIa complexes supporting fibrinogen binding. Platelet aggregation in response to C1q multimers was accompanied by the aspirin-inhibitable release of granule contents and P-selectin (CD62) expression. Platelet aggregation was inhibited by the collagenous domain of C1q (c-Clq) and a monoclonal antibody directed against C1q receptors, suggesting the direct involvement of the 67-kD platelet C1qR. Antibodies against the very late antigen 2 or CD36 collagen receptors were without effect. Platelet exposure to C1q multimers was also accompanied by the expression of procoagulant activity, as demonstrated by the dose-dependent shortening of the kaolin recalcification time of normal plasma from 108 +/- 12 s in the presence of unstimulated platelets to 62 +/- 14 s in the presence of platelets that had been preincubated (5 min, 37 degrees C) with 100 micrograms/ml multimeric C1q (n = 3). These data suggest that platelet interactions with C1q multimers or immobilized C1q, resulting in the activation of GPIIb-IIIa fibrinogen binding sites and the expression of P-selectin as well as platelet procoagulant activity, are likely to contribute to thrombotic events associated with complement activation and inflammation.

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Selected References

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