A monoclonal anti-human platelet antibody: a new platelet aggregating substance.
A monoclonal anti-human platelet antibody, TP82, is described, which caused irreversible aggregation of platelets in association with the release of adenosine triphosphate or [14C] serotonin, and which inhibited ristocetin-induced agglutination. Immunofluorescence assay showed that the antibody binds to platelets, 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 ethylendiaminotetraacetate, diltiazem, W-7, PGE1, and several metabolic inhibitors. At a concentration of apyrase or CP/CPK, which inhibited adenosine 5-diphosphate-induced aggregation. TP82-induced aggregation was only partially affected. Thrombin was not required for the antibody-mediated effects, since two 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-molecular-weight binding site on the platelet membrane.
D000255:Adenosine Triphosphate / Q000097:blood; D000818:Animals; D000911:Antibodies, Monoclonal / Q000032:analysis / Q000502:physiology*; D000918:Antibody Specificity; D001667:Binding, Competitive; D001792:Blood Platelets / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D066298:In Vitro Techniques; D007770:L-Lactate Dehydrogenase / Q000097:blood; D051379:Mice; D010974:Platelet Aggregation / Q000187:drug effects; D012310:Ristocetin / Q000494:pharmacology; D012701:Serotonin / Q000097:blood; D013929:Thromboxane B2 / Q000096:biosynthesis
D000911:Antibodies, Monoclonal; D012310:Ristocetin; D012701:Serotonin; D013929:Thromboxane B2; D000255:Adenosine Triphosphate; D007770:L-Lactate Dehydrogenase