Effect of anti-P1A1 antibody on human platelets. II. Mechanism of the complement-dependent release reaction.
We studied the mechanism by which complement activated by anti-P1A1 antibody elicits the platelet release reaction. Anti-P1A1 antibody mediates its action through the classic complement pathway, and its effect depends on the concentration of IgG antibody on the platelet surface. At relatively high concentrations of anti-P1A1 antibody the release reaction was mediated by a mechanism in part independent of extracellular ADP and metabolic energy and inhibited by only high concentrations of PGE1. However, at lower concentrations of anti-P1A1 antibody the release reaction was dependent on metabolic energy and ADP, and the concentration of PGE1 required to inhibit platelet release was similar to that required to inhibit ADP-induced release. The cyclooxygenase inhibitor acetylsalicylic acid inhibited the release reaction at all nonlytic antibody levels studied. None of the agents studied inhibited the induction of platelet lysis by very high concentrations of anti-P1A1 antibody, and no effect of antibody on platelet 14C-serotonin uptake was observed at antibody concentrations that did not mediate direct in vitro alteration. These studies suggest the possible use of pharmacologic agents in modifying some complement-mediated platelet alterations.
D000244:Adenosine Diphosphate / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000378:metabolism; D000906:Antibodies; D001241:Aspirin / Q000494:pharmacology; D001792:Blood Platelets / Q000276:immunology* / Q000378:metabolism; D003165:Complement System Proteins / Q000276:immunology*; D006801:Humans; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology; D010978:Platelet Factor 4 / Q000378:metabolism; D011458:Prostaglandins E / Q000494:pharmacology; D012701:Serotonin / Q000378:metabolism
D000906:Antibodies; D010726:Phosphodiesterase Inhibitors; D011458:Prostaglandins E; D012701:Serotonin; D010978:Platelet Factor 4; D000244:Adenosine Diphosphate; D000255:Adenosine Triphosphate; D003165:Complement System Proteins; D001241:Aspirin