ANTI-GPIIB/IIIA (CD41) MONOCLONAL ANTIBODY-INDUCED PLATELET ACTIVATION REQUIRES FC RECEPTOR-DEPENDENT CELL CELL-INTERACTION

We studied platelet activation by UR1, a murine IgG1 anti-CD41 mAb. Like thrombin and crosslinked anti-Fc-gamma-RII mAb IV3, UR1 initiates prompt aggregation and Ca2+ mobilization. UR1 F(ab')2 fragments failed to activate, yet inhibited UR1 IgG-mediated activation. UR1-induced activation was blocked by anti-Fc-gamma-RII mAb. High viscosity (15% dextran or Ficoll), which impedes cell-cell interaction, inhibited activation by UR1. Cell-cell interaction was confirmed by cell-mixing studies. UR1 binding to platelets of one pool was blocked with UR1 F(ab')2 allowing UR1 binding only to Fc-gamma-RII. IV3 Fab fragments blocked ligand binding to Fc-gamma-RII on platelets of a second pool: thus, UR1 could bind only its epitope. URI initiated an immediate [Ca2+], increase in the intermixed pools at low ionic strength. These studies indicate that UR1 IgG binds CD41 on one platelet to form immune complexes which then crosslink and stimulate Fc-gamma-RII on nearby platelets. Two other anti-CD41 mAb, 6C9 and C17, and two anti-CD9 mAb, AG1 and mAb7, activated platelets in a UR1-like manner. We propose that platelet Fc-gamma-RII crosslinking that follows the interaction of IgG-opsonized platelets may be a common mechanism by which anti-platelet antibodies activate platelets.