Effects of various inhibitors on platelet activation induced by TP 82, a CD 9 monoclonal antibody

Abstract TP 82, a monoclonal antibody against CD 9 antigen, induced human platelet activation at concentrations higher than 0.4 μg/mL in terms of aggregation, release of intracellular granule contents, production of arachidonic acid metabolites, and elevation of the intracellular Ca 2+ concentration. The effects of a competitive inhibitor of ADP, acetylsalicylic acid, EGTA, and GRGDSP which blocks fibrinogen binding to IIb/IIIa complex suggested that each of released ADP, thromboxane A 2 , extra-cellular Ca 2+ , and close cell contact acts together to potentiate platelet activation induced by TP 82. While each of these inhibitors severely suppressed platelet activation induced by lower concentrations of the antibody (≦0.8 μ g/mL), that induced by higher concentrations ( ≧3.2 μ g/mL ) was only partially blocked. Intracellular Ca 2+ elevation was totally dependent upon the production of thromboxane A 2 , regardless of the antibody concentrations.