Monoclonal antibodies against human platelet glycoprotein IIIa

Abstract

Two murine monoclonal antibodies specific for human platelets were prepared and characterized by immunofluorescence, immunoprecipitation and by studying their effect on platelet function. Immunoprecipitation with lysates of normal platelets and platelets from a patient with Glanzmann's thrombasthenia revealed that the monoclonal antibodies were directed against glycoprotein GP IIIa. One of these anti-GP-IIIa antibodies (C17) inhibited both ADP- and collagen-induced platelet aggregation as well as ADP-induced fibrinogen binding to platelets. The other anti-GP-IIIa antibody (C15) also caused a complete inhibition of aggregation with collagen. However, a small, and fully reversible, 'primary wave' was observed if the platelets were stimulated with ADP when platelet-rich plasma was used. The ability to bind fibrinogen was unimpaired for platelets incubated with C15. These findings show that C15 and C17 probably recognize different determinants on GP IIIa. Neither of the monoclonal anti-GP-IIIa antibodies blocked the binding to Zwa-positive platelets of human polyclonal anti-Zwa antibodies. This implies that Zwa is different from the epitopes recognized by C15 and C17.