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 Fc gamma RII receptor. There is almost no information on Fc gamma RII 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 con centrations of the antiprotein disulfide isomerase antibody as low as 25 to 40 mu g/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 Fc gamma RII (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 E-1, and Ethylenediaminetetraacetic 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. (C) 1999 Elsevier Science Ltd. All rights reserved.