A MONOCLONAL ANTI-HUMAN PLATELET ANTIBODY - A NEW PLATELET AGGREGATING SUBSTANCE

  • 1 January 1985
    • journal article
    • research article
    • Vol. 65  (2) , 382-391
Abstract
A monoclonal anti-human platelet antibody, TP82, is described, which caused irreversible aggregation of platelets in association with the release of ATP or [14C] serotonin, and which inhibited ristocetin-induced agglutination. Immunofluorescence assay showed that the antibody binds to platetes, megakaryocytes and common acute lymphoblastic leukemia cells. The antibody (IgG1) immunoprecipitated a polypeptide of 23,000 daltons with an isoelectric point of about 7.0. The aggregation induced by the purified antibody and/or F(ab'')2 fragments occurred in platelet-rich plasma and with washed platelets, but not with formalin-fixed washed platelets. TP82-induced aggregation was completely inhibited by disodium ethylenediaminotetraacetate, diltiazem, W-7, PGE [prostaglandin E-1], and several metabolic inhibitors. At a concentration of apyrase or CP/CPK [creatine phosphate/creatine phosphokinase], which inhibited ADP induced aggregation, TP82-induced aggregation was only partially affected. Thrombin was not required for the antibody-mediated effects, since 2 thrombin inhibitors failed to block the reaction. The antibody, at least at a high concentration, induced platelet aggregation by a mechanism almost independent of thromboxane A2 formation, since cyclooxygenase inhibitors had little inhibitory effect on aggregation. TP82 monoclonal antibody is a new platelet-aggregating substance that interacts with a low-MW binding site on the platelet membrane.