Complement proteins C5b-9 stimulate procoagulant activity through platelet prothrombinase.
The capacity of platelets treated with nonlytic concentrations of the C5b-9 proteins to catalyze prothrombin activation and thereby trigger clot formation has been investigated. When suspended in the presence of exogenous factors Xa and Va, gel-filtered platelets treated with purified C5b-9 proteins catalyzed prothrombin to thrombin conversion at rates up to tenfold above controls, and exceeded by up to fourfold the prothrombinase activity observed for thrombin-stimulated platelets. In the absence of added factor Va, C5b-9 assembly on the platelet surface significantly shortened the lag period before prothrombinase expression that was observed for untreated platelets and increased the maximum catalytic rate of thrombin formation. A comparison with other platelet stimuli revealed that the C5b-9-induced activation of platelet prothrombinase closely paralleled the effects mediated by calcium ionophore A23187. Our data suggest that the C5b-9 proteins promote the release of platelet factor V and the assembly of the prothrombinase complex, thereby potentiating the effects of thrombin on the activation of prothrombinase. Membrane assembly of the C5b-9 proteins was also observed to markedly accelerate the rate of platelet-catalyzed plasma clotting, suggesting a direct link between C5b-9-mediated prothrombinase activation and procoagulant activity accompanying immunologic damage to the platelet.
D001777:Blood Coagulation; D001792:Blood Platelets / Q000201:enzymology* / Q000502:physiology; D000001:Calcimycin / Q000494:pharmacology; D015938:Complement Membrane Attack Complex; D003165:Complement System Proteins / Q000502:physiology*; D004789:Enzyme Activation; D006801:Humans; D010978:Platelet Factor 4 / Q000378:metabolism; D013917:Thrombin / Q000378:metabolism; D013925:Thromboplastin / Q000378:metabolism*
D015938:Complement Membrane Attack Complex; D010978:Platelet Factor 4; D000001:Calcimycin; D003165:Complement System Proteins; D013925:Thromboplastin; D013917:Thrombin