Characterization of the Fcγ receptor on human platelets

Abstract

IgG-containing immune complexes may play a role in the immune destruction of human platelets by interacting with an Fcγ receptor on the platelet surface. We studied the platelet Fcγ receptor and characterized its interaction with IgG ligand and anti-Fcγ receptor monoclonal antibodies. Oligomers of IgG, but not monomeric IgG, bound to platelets and the number of binding sites was significantly increased at low ionic strength. Ligand-binding studies indicated that normal human platelets express a single Fcγ receptor (FcγRII) with 8559 ± 852 sites per cell, K d = 12.5 ± 1.7 × 10 −8 M using trimeric IgG. Results of studies with bivalent and Fab monoclonal anti-FcγRII were consistent with each Fcγ receptor expressing two epitopes recognized by the antibody. The number of Fcγ binding sites and affinity of binding were unchanged by the presence of 2.0 m M Mg 2+ or 10 μg/ml cytochalasin B. Platelet stimulation with thrombin or ADP in the presence of fibrinogen also did not alter the number of Fcγ binding sites or the affinity of binding. However, platelets preincubated with 5 μ M dexamethasone expressed a decreased number of Fcγ binding sites as well as decreased IgG-dependent platelet aggregation. Platelets from patients with Glanzmann's thrombasthenia and from patients with the Bernard Soulier syndrome expressed a normal number and affinity of Fcγ binding sites. The data suggest that platelet FcγRII binding of trimeric IgG occurs independent of actin filament interaction, Mg 2+, ADP, or thrombin and does not require GPIIb/IIIa or GPIIb/IIIa-fibrinogen interaction. Furthermore, this receptor appears to be normally expressed on GPIb-deficient platelets and susceptible to modulation by glucocorticoids. Finally, the Fcγ-binding protein was isolated from whole platelets as a 220-kDa protein which upon reduction dissociates into 50,000 M r Subunits.