Monoclonal antibodies against human platelet membrane glycoproteins IIb-IIIa. II. Different effects on platelet function
Heinrich, D.; Scharf, T.; Santoso, S.; Clemetson, K.J.; Mueller-Eckhardt, C.
Thrombosis Research 38(5): 547-559
1985
ISSN/ISBN: 0049-3848 PMID: 2409615 Document Number: 252822
Preincubation of human platelets with 2 pairs of immunologically identical monoclonal antibodies (mab) directed against epitopes on the membrane glycoprotein IIb-IIIa complex 2 of them (Gi3 and Gi5) precipitating glycoproteins IIb-IIIa, and 2 (Gi4 and Gi6) recognizing glycoprotein IIIa-induced slightly different inhibitory effects on platelet function. Gi3 and Gi5 blocked platelet aggregation and 14C-serotonin release from platelets induced by ADP, collagen, thrombin, arachidonic acid, ionophore A 23187, platelet activating factor and ristocetin (in the presence of divalent ions). Ristocetin-induced platelet agglutination (in the presence of EDTA) was not inhibited by these mab. Gi4 had no effect on platelet aggregation and release. Gi6 had the same effect on platelet function as Gi3 and Gi5, but only when incubated with Zw(a) (PIA1)-positive platelets with the exception that collagen-induced aggregation was not affected. The similar, though not identical, effects on platelet function induced by mab against different epitopes on the glycoprotein complex IIb-IIIa indicate an unspecific interference with platelet membrane function possibly due to steric hindrance by mab of the fibrinogen receptor or by inhibition of conformational changes in the GP IIb-IIIa complex necessary for exposure of the fibrinogen binding site.