[Inhibition of Fc-receptor dependent platelet aggregation by monoclonal antibodies against the glycoprotein IIb-IIIa complex].
A murine monoclonal antibody (MoAb) VM16a specifically binding to human platelets has been produced. Approximately 56,000 molecules of VM16a bound per platelet at saturation (Kd = 7.9 nM) but no binding to platelets from Glanzmann's thrombasthenia patients was detected. VM16a precipitated two proteins with molecular masses corresponding to those of glycoproteins (GP) IIb and IIIa from solubilized surface-labelled platelets. However, after dissociation of the GPIIb--IIIa complex with EDTA VM16a did not bind to platelets and precipitated nothing from their lysate, thus evidencing that its determinant is complex-dependent. VM16a had no effect on ADP-, thrombin- and ristocetin-induced platelet aggregation but inhibited the aggregation induced by collagen. This inhibitory effect was more pronounced in the presence of plasma. VM16a completely blocked the Fc-receptor-mediated aggregation induced by aggregated human IgG, aggregated murine IgG1 and the previously described MoAb VM58. F(ab')2 fragments of VM16a were also able to inhibit this aggregation by decreasing the rate of aggregation induced by aggregated IgG and by extending the lag phase of VM58-induced aggregation. These results suggest that the platelet Fc-receptor may be topographically associated with the GPIIb-IIIa complex.
Vinogradov
D V
DV
Department of Medicine, Sidney University, Australia.
Vlasik
T N
TN
Agafonova
O G
OG
Vasil'ev
S A
SA
Lagutina
N Ia
NIa
Makarov
V A
VA
Berndt
M
M
Mazurov
A V
AV
D000244:Adenosine Diphosphate / Q000494:pharmacology; D000911:Antibodies, Monoclonal / Q000276:immunology*; D006801:Humans; D010974:Platelet Aggregation / Q000187:drug effects*; D010975:Platelet Aggregation Inhibitors; D010980:Platelet Membrane Glycoproteins / Q000276:immunology*; D011233:Precipitin Tests; D011961:Receptors, Fc / Q000378:metabolism*; D012310:Ristocetin / Q000494:pharmacology; D013917:Thrombin / Q000494:pharmacology
D000911:Antibodies, Monoclonal; D010975:Platelet Aggregation Inhibitors; D010980:Platelet Membrane Glycoproteins; D011961:Receptors, Fc; D012310:Ristocetin; D000244:Adenosine Diphosphate; D013917:Thrombin
Ingibirovanie Fc-retseptorzavisimoĭ agregatsii trombotsitov monoklonal'nom antitelom protiv kompleksa glikoproteinov IIb-IIIa.