Monoclonal antibodies against human platelet membrane glycoproteins IIb-IIIa. II. Different effects on platelet function.
Preincubation of human platelets with two pairs of immunologically identical monoclonal antibodies (mab) directed against epitopes on the membrane glycoprotein IIb-IIIa complex - two of them (Gi3 and Gi5) precipitating glycoproteins IIb-IIIa, and two (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) (PlAl)-positive platelets with the exception that collagen-induced aggregation was not affected. We conclude that 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.
Heinrich
D
D
Scharf
T
T
Santoso
S
S
Clemetson
K J
KJ
Mueller-Eckhardt
C
C
D000911:Antibodies, Monoclonal / Q000276:immunology*; D001792:Blood Platelets / Q000502:physiology*; D003094:Collagen / Q000494:pharmacology; D000939:Epitopes / Q000276:immunology; D006023:Glycoproteins / Q000276:immunology*; D006801:Humans; D066298:In Vitro Techniques; D008565:Membrane Proteins / Q000276:immunology*; D010974:Platelet Aggregation; D010980:Platelet Membrane Glycoproteins; D011956:Receptors, Cell Surface / Q000378:metabolism; D012310:Ristocetin / Q000494:pharmacology; D012701:Serotonin / Q000378:metabolism
D000911:Antibodies, Monoclonal; D000939:Epitopes; D006023:Glycoproteins; D008565:Membrane Proteins; D010980:Platelet Membrane Glycoproteins; D011956:Receptors, Cell Surface; D012310:Ristocetin; D012701:Serotonin; D003094:Collagen