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Anti‐GPIIb/IIIa (CD41) monoclonal antibody‐induced platelet activation requires Fc receptor‐dependent cell‐cell interaction
Author(s) -
Anderson George P.,
Winkel Jan G. J. van,
Anderson Clark L.
Publication year - 1991
Publication title -
british journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.907
H-Index - 186
eISSN - 1365-2141
pISSN - 0007-1048
DOI - 10.1111/j.1365-2141.1991.tb08010.x
Subject(s) - platelet , chemistry , platelet activation , monoclonal antibody , epitope , thrombin , microbiology and biotechnology , receptor , antibody , platelet membrane glycoprotein , biophysics , biochemistry , immunology , biology
We studied platelet activation by UR1, a murine IgG1 anti‐CD41 mAb. Like thrombin and crosslinked anti‐FcγRII mAb IV3, UR1 initiates prompt aggregation and Ca 2+ mobilization. UR1 F(ab′) fragments failed to activate, yet inhibited UR1 IgG‐mediated activation. UR1‐induced activation was blocked by anti‐FcγRII 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 FcγRII. IV3 Fab fragments blocked ligand binding to FcγRII on platelets of a second pool; thus, UR1 could bind only its epitope. UR1 initiated an immediate [Ca 2+ ] 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 FcγRII 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 FcγRII crosslinking that follows the interaction of IgG‐opsonized platelets may be a common mechanism by which antiplatelet antibodies activate platelets.