Myeloperoxidase-mediated platelet release reaction.
The ability of the neutrophil myeloperoxidase-hydrogen peroxide-halide system to induce the release of human platelet constituents was examined. Both lytic and nonlytic effects on platelets were assessed by comparison of the simultaneously measured release of a dense-granule marker, [(3)H]serotonin, and a cytoplasmic marker, [(14)C]adenine. Incubation of platelets with H(2)O(2) alone (20 muM H(2)O(2) for 10 min) resulted in a small, although significant, release of both serotonin and adenine, suggesting some platelet lysis. Substantial release of these markers was observed only with increased H(2)O(2) concentrations (>0.1 mM) or prolonged incubation (1-2 h). Serotonin release by H(2)O(2) was markedly enhanced by the addition of myeloperoxidase and a halide. Under these conditions, there was a predominance of release of serotonin (50%) vs. adenine (13%), suggesting, in part, a nonlytic mechanism. Serotonin release by the complete peroxidase system was rapid, reaching maximal levels in 2-5 min, and was active at H(2)O(2) concentrations as low as 10 muM. It was blocked by agents which inhibit peroxidase (azide, cyanide), degrade H(2)O(2) (catalase), chelate Mg(2+) (EDTA, but not EGTA), or inhibit platelet metabolic activity (dinitrophenol, deoxyglucose).These results suggest that the myeloperoxidase system initiates the release of platelet constituents primarily by a nonlytic process analogous to the platelet release reaction. Because components of the peroxidase system (myeloperoxidase, H(2)O(2)) are secreted by activated neutrophils, the reactions described here may have implications for neutrophilplatelet interaction in sites of thrombus formation.
D000225:Adenine / Q000097:blood; D000328:Adult; D000963:Antimetabolites / Q000494:pharmacology; D001792:Blood Platelets / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure; D002614:Chelating Agents / Q000494:pharmacology; D002712:Chlorides / Q000494:pharmacology; D004347:Drug Interactions; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology; D066298:In Vitro Techniques; D009195:Peroxidase / Q000494:pharmacology*; D010544:Peroxidases / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D012701:Serotonin / Q000097:blood; D013997:Time Factors
D000963:Antimetabolites; D002614:Chelating Agents; D002712:Chlorides; D012701:Serotonin; D006861:Hydrogen Peroxide; D010544:Peroxidases; D009195:Peroxidase; D000225:Adenine