A polyclonal antibody to protein disulfide isomerase induces platelet aggregation and secretion

Monoclonal mouse antiplatelet antibodies against a variety of platelet surf ace components can activate platelets, causing platelet aggregation and sec retion. The mechanism involves binding of the Fab domain to a platelet surf ace antigen, and the activation occurs through an interaction of the Fc dom ain with the platelet Fc gamma RII receptor. There is almost no information on Fc gamma RII receptor-dependent activation of platelets by polyclonal r abbit antibodies. We presently report that a polyclonal rabbit antibody to a platelet surface antigen, protein disulfide isomerase, induces platelet a ggregation and secretion, These effects are seen with con centrations of th e 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 an tibody do not cause aggregation. Fab made from the rabbit antiprotein disul fide isomerase antibody as well as a monoclonal antibody to the Fc gamma RI I (IV.3) receptor block the aggregation and secretion responses, Aggregatio n and secretion are inhibited by an antiglycoprotein IIbIIIa antibody, whic h blocks fibrinogen binding and wortmannin, an inhibitor of phosphoinositid e 3-kinase, Aspirin, prostaglandin E-1, and Ethylenediaminetetraacetic acid (EDTA) also block the platelet responses. These data suggest that activati on of platelets by polyclonal antibodies occurs by mechanisms similar to th ose found with activating monoclonal antibodies. (C) 1999 Elsevier Science Ltd. All rights reserved.