Effect of heterologous antiplatelet antibody on human platelets: a new pathway to platelet alteration

Abstract

Heterologous monomeric IgG anti-human platelet antibody mediates platelet aggregation and release of 14 C-serotonin from human platelets. The reaction is independent of complement and thrombin and is not inhibited by acetylsalicylic acid. Studies are presented showing that when adenosine diphosphate (ADP) was removed by apyrase, creatine phosphokinase, or pyruvate kinase, antibody-induced aggregation and serotonin release were only inhibited 50% and 35%, respectively. Inhibition of both aerobic metabolism with antimycin A (5.0 μg/ml) and anaerobic glycolysis with 2-deoxyglucose (10 mM) completely prevented ADP and thrombin-induced aggregation and release. However, inhibition of antibody-mediated aggregation and release was incomplete at high concentrations of antibody. Dibutyryl cyclic adenosine 3’,5’-monophosphate (cAMP) inhibited antibody-induced aggregation and release in a dose-related fashion, but required tenfold the concentration necessary to inhibit the effect of ADP. Prostaglandin E1, which stimulates adenylate cyclase to form cAMP, inhibited the antibody effects 50% at 50-fold the concentration required for equivalent inhibition of aggregation and release by epinephrine. The phosphodiesterase inhibitor SH869 (2 μM) gave similar results. These data suggest that heterologous antibody (IgG)-induced platelet aggregation and release are mediated in part by a mechanism independent of extracellular ADP and in part independent of metabolic energy. The high concentration of cAMP required for inhibition suggests a pathway distinct from that mediated by ADP, epinephrine, or thrombin.