The Fluid-phase SC5b-9 Terminal Complement Complex Binds to the GPIIb/IIIa Complex of Thrombin-stimulated Human Blood Platelets Inhibiting Platelet Aggregation.

We have investigated interactions between human blood platelets and the vitronectin-containing fluid-phase terminal complement complex, the SC5b-9, which is a non-cytolytic variant of the membrane attack complex C%9(m). SC5b-9 affinity for the platelet membrane glycoprotein IIb/IIIa (GPIIb/IIIa) complex was demonstrated by crossed radio-immunoelectrophoresis of solubilized, washed platelets followed by incubation of the immunoplates with (125)I-labelled SC5b-9 and exposure to X-ray films. Platelet adhesion to surfaces of polystyrene coated with the SC5b-9 complex was studied under static conditions in an enzyme immunoassay (EIA). Thrombin-stimulated platelets but not non-stimulated platelets adhered to the SCSb-9coated surface, and platelet adherence was inhibited in a dose-dependent manner by the tetrapeptide RGDS (Arg-Gly-Asp-Ser). This indicates an interaction between platelet GPIIb/IIIa and an RGD sequence in SC5b-9, possibly in its vitronectin moiety. The effect of the SC5b-9 complex on platelet aggregation was examined in a dual-channel aggregometer. Here the SC5b-9 complex inhibited both ADP-and thrombin-induced platelet aggregation in a dose-dependent manner. These results were confirmed by electron microscopical examination of the contents of the aggregometer cuvettes. Platelets which had been thrombin-stimulated in the presence of SC5b-9 appeared activated and had undergone secretion, but showed no aggregation. By contrast, platelets from the control experiments which had been thrombin-stimulated in the absence of SC5b-9 were aggregated. To the best of our knowledge, this is the 6rst report on a biological role of the SC5b-9 complex in platelet function.