Characterization of human platelet IgG Fc receptor associated with membrane glycoprotein.

Human platelets express IgG Fc receptors (Fc gamma R). Previously we reported that circulating immune complexes (CIC) inhibited fibrinogen binding to platelet glycoprotein IIb/IIIa complex (GPIIb/IIIa) and that isolated Fc gamma R were recognized by monoclonal antibodies (mAb's) to GPIIb and GPIIIa (J.Lab. Clin. Med. 117:209-217, 1991). In this study, we further characterized the properties of the Fc gamma R and the activity associated with GPIIb/IIIa. Binding of Fc portion of human IgG (Fc) to the platelet Fc gamma R associated with GPIIb/IIIa complex, unlike fibrinogen receptor, did not require divalent cations. The Fc gamma R bound to immobilized immune complex were recognized by mAb's to GPIIb, GPIIIa, GPIIb/IIIa. Preincubation of platelet extract with fibrinogen inhibited the binding of heat-aggregated IgG (HAG) to the extract. Flow cytometry of whole platelets revealed inhibition of mAb binding to GPIIb/IIIa, when platelets were incubated with Fc fragments or HAG. Using platelet extract coated to microtiter plates, similar findings were noted with Fc and HAG. The dissociation of GPIIb/IIIa complex by incubating platelet extract at 37 degrees C in the presence of EDTA caused a marked decrease in the binding of GPIIb and GPIIIa to the immobilized immune complex. Activation of intact platelets with ADP resulted in an increased binding of HAG to the platelets, indicating that an augmented Fc gamma R activity is associated with the activation of GPIIb/IIIa. These results suggest a close relationship of the Fc gamma R activity to the fibrinogen binding site (GPIIb/IIIa complex).