Monoclonal Antibodies Bound to Subunits of the Integrin GPIIb-IIIa Are Internalized and Interfere With Filopodia Formation and Platelet Aggregation

The monoclonal antibodies Tab and AP3 are directed, respectively, against GPllb and GPllla, the subunits of the platelet fibrinogen receptor. When added together to platelets, these antibodies prevent adenosine diphosphate (ADPI-induced platelet aggregation, despite normal fibrinogen binding (Newman et al. Blood 69:668, 1987). To explore the cellular requirements of aggregation after fibrinogen binding, we used several techniques to study platelets treated with Tab and AP3, then stimulated with ADP. We used scanning and transmission electron microscopy to evaluate platelet morphology, immunolabelsurface replication to determine whether individual GPllbllla complexes clustered, immunocytochemistry on frozen thin sections to study the subcellular distribution of the integrin GPllb-llla and fibrinogen, and biochemical methods