A polyclonal antibody to protein disulfide isomerase induces platelet aggregation and secretion.
Monoclonal mouse antiplatelet antibodies against a variety of platelet surface components can activate platelets, causing platelet aggregation and secretion. The mechanism involves binding of the Fab domain to a platelet surface antigen, and the activation occurs through an interaction of the Fc domain with the platelet FcgammaRII receptor. There is almost no information on FcgammaRII receptor-dependent activation of platelets by polyclonal rabbit antibodies. We presently report that a polyclonal rabbit antibody to a platelet surface antigen, protein disulfide isomerase, induces platelet aggregation and secretion. These effects are seen with concentrations of the antiprotein disulfide isomerase antibody as low as 25 to 40 microg/mL. Fab and F(ab')2 preparations of the rabbit antiprotein disulfide isomerase antibody do not cause aggregation. Fab made from the rabbit antiprotein disulfide isomerase antibody as well as a monoclonal antibody to the FcgammaRII (IV.3) receptor block the aggregation and secretion responses. Aggregation and secretion are inhibited by an antiglycoprotein IIbIIIa antibody, which blocks fibrinogen binding and wortmannin, an inhibitor of phosphoinositide 3-kinase. Aspirin, prostaglandin E1, and Ethylenediamine-tetraacetic acid (EDTA) also block the platelet responses. These data suggest that activation of platelets by polyclonal antibodies occurs by mechanisms similar to those found with activating monoclonal antibodies.
Essex
D W
DW
Department of Medicine, State University of New York, Downstate Medical Center, Brooklyn, 11203, USA. dessex@netmail.hscbklyn.edu
Li
M
M
D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D000925:Anticoagulants / Q000494:pharmacology; D001792:Blood Platelets / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D007106:Immune Sera / Q000494:pharmacology; D007140:Immunoglobulin Fab Fragments / Q000494:pharmacology; D007074:Immunoglobulin G / Q000302:isolation & purification / Q000378:metabolism* / Q000494:pharmacology; D008297:Male; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology; D015539:Platelet Activation / Q000187:drug effects / Q000502:physiology*; D010974:Platelet Aggregation / Q000187:drug effects / Q000502:physiology*; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000276:immunology; D019704:Protein Disulfide-Isomerases / Q000276:immunology*; D011817:Rabbits; D017452:Receptors, IgG / Q000037:antagonists & inhibitors
D000911:Antibodies, Monoclonal; D000925:Anticoagulants; D007106:Immune Sera; D007140:Immunoglobulin Fab Fragments; D007074:Immunoglobulin G; D010726:Phosphodiesterase Inhibitors; D010975:Platelet Aggregation Inhibitors; D019039:Platelet Glycoprotein GPIIb-IIIa Complex; D017452:Receptors, IgG; D019704:Protein Disulfide-Isomerases