On the mechanism by which complement proteins C5b-9 increase platelet prothrombinase activity.
Membrane assembly of complement proteins C5b-9 on human platelets results in a dose-dependent increase in the binding of coagulation factors Va and Xa to the plasma membrane, concomitant with a marked increase in platelet prothrombinase activity. Factor Va binding increased by 6-15-fold in platelets treated with the C5b-9 proteins as compared to controls. In the presence of near-saturating concentrations of factor Xa, factor Va binding to C5b-9-treated platelets approximately doubled. In the absence of added factor Va, C5b-9-treated platelets bound 1700 molecules of factor Xa versus 50 molecules/cell bound to controls, suggesting that C5b-9 assembly on the platelet surface initiates the release of platelet factor V from the alpha-granules. The capacity of the C5b-9 proteins to initiate the nonlytic release of the platelet alpha-granule storage pool was confirmed by assay for platelet factor 4. When measured in the presence of exogenous factor Va (2 micrograms/ml), factor Xa uptake by C5b-9 platelets increased to approximately 5500 molecules/cell (versus 330 molecules/cell for controls). Removal of external Ca2+ inhibited the C5b-9-initiated release of the alpha-granule storage pool and reduced by approximately 50% the expression of new factor Va binding sites, suggesting that these two events contributing to increased platelet prothrombinase activity are mediated in part by the influx of Ca2+ across the C5b-9 pore.
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D000818:Animals; D001792:Blood Platelets / Q000201:enzymology*; D002417:Cattle; D015938:Complement Membrane Attack Complex; D003165:Complement System Proteins / Q000378:metabolism*; D005165:Factor V / Q000378:metabolism*; D015943:Factor Va; D005170:Factor X / Q000378:metabolism*; D015951:Factor Xa; D006801:Humans; D007700:Kinetics
D015938:Complement Membrane Attack Complex; C022475:prothrombinase complex; D015943:Factor Va; D005165:Factor V; D005170:Factor X; D003165:Complement System Proteins; D015951:Factor Xa