Monoclonal antibodies against platelet membrane glycoproteins. Characterization and effect on platelet function.
The specificity of five monoclonal antibodies (P1-P6) against platelet surface components was determined by immunoprecipitation of surface-labelled platelets from normal donors and patients with known platelet glycoprotein defects, followed by analysis by gel electrophoresis. Three (P2, P4 and P6) precipitated glycoproteins IIb and IIIa and, in addition, P2 precipitated glycoprotein Ia. P1 precipitated normally only glycoprotein Ib also Ia when the platelets were pretreated with neuraminidase. P3 precipitated principally glycoprotein Ia but glycoprotein Ib was also weakly precipitated. The effects of the monoclonals on platelet function were tested. P1 and P2 completely inhibited and P3 slightly inhibited thrombin-induced platelet aggregation. P2 also inhibited collagen-induced aggregation and partially inhibited ADP-induced platelet aggregation. P3, P4 and P6 partially inhibited ADP-induced platelet aggregation. None had any effect on ristocetin-induced aggregation despite P1 and P3 binding to glycoprotein Ib. These results confirm the role of glycoproteins IIb and IIIa in aggregation induced by various agents and suggest that the function of glycoprotein Ib in thrombin-induced aggregation is more important than previously suspected and that glycoprotein Ia may also be involved in platelet functions.
D000818:Animals; D000911:Antibodies, Monoclonal / Q000302:isolation & purification*; D001792:Blood Platelets / Q000276:immunology* / Q000502:physiology; D001798:Blood Proteins / Q000276:immunology*; D006023:Glycoproteins / Q000276:immunology* / Q000302:isolation & purification; D006801:Humans; D007120:Immunochemistry; D008297:Male; D008565:Membrane Proteins / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D011485:Protein Binding
D000911:Antibodies, Monoclonal; D001798:Blood Proteins; D006023:Glycoproteins; D008565:Membrane Proteins