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. UR1 initiated an immediate [Ca2+]i 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.
Anderson
G P
GP
Department of Internal Medicine, Ohio State University College of Medicine, Columbus.
van de Winkel
J G
JG
Anderson
C L
CL
D000911:Antibodies, Monoclonal / Q000276:immunology; D000943:Antigens, Differentiation / Q000276:immunology*; D001792:Blood Platelets / Q000276:immunology / Q000378:metabolism; D002118:Calcium / Q000097:blood; D002450:Cell Communication / Q000276:immunology; D006801:Humans; D015539:Platelet Activation / Q000276:immunology*; D010974:Platelet Aggregation / Q000276:immunology; D010980:Platelet Membrane Glycoproteins / Q000276:immunology*; D011961:Receptors, Fc / Q000276:immunology*; D017452:Receptors, IgG; D014783:Viscosity
D000911:Antibodies, Monoclonal; D000943:Antigens, Differentiation; D010980:Platelet Membrane Glycoproteins; D011961:Receptors, Fc; D017452:Receptors, IgG; D002118:Calcium