The interaction of human neutrophils and platelets in vitro was examined, with emphasis on the ability of the neutrophil products, myeloperoxidase, and hydrogen peroxide, to initiate release of platelet constituents. Neutrophils activated by phagocytosis induced the release of radiolabeled serotinin and adenine from platelets. Phagocytosis was required, and release was blocked by the omission of halides or the addition of catalase. No release of serotonin or adenine was observed when neutrophils deficient in myeloperoxidase (hereditary myeloperoxidase deficiency) or oxidative metabolism (chronic granulomatous disease) were used, but release was restored to normal levels by the addition of purified myeloperoxidase on an H2O2-generating system, respectively, to the defective neutrophils. These data clearly implicate the myeloperoxidase-H2O2-halide system. Paradoxically, the heme enzyme inhibitors, azide and cyanide, failed to inhibit and, in fact, enhanced release. This enhancement was observed in the presence of normal and myeloperoxidase-deficient neutrophils, but not with chronic granulomatous disease neutrophils and was, therefore, dependent on H2O2, but not peroxidase. A peroxide-generating enzyme, glucose oxidase or reagent H2O2 (>10 mM), caused the release of serotonin and adenine. These effects were inhibited by catalase and enhanced by azide, cyanide, and aminotriazole, the latter stimulation being especially prominent in the presence of exogenous catalase. Thus, the enhancement by heme enzyme inhibitors of release by H2O2 or activated PMN appeared to be a consequence of the inhibition of platelet catalase. The presence of catalase in platelets was demonstrated by enzyme assay and by the inhibition by platelets of H2O2-dependent myeloperoxidase-catalyzed protein iodination. These studies demonstrate that neutrophils activated by phagocytosis can induce the release of platelet constituents and that this is mediated by the secretion of myeloperoxidase and hydrogen peroxide. The peroxidase-catalyzed reaction predominates, except in the presence of heme enzyme inhibitors that block both peroxidase and platelet catalase, thereby allowing a nonenzymatic effect of H2O2 alone to be manifest.
|Original language||English (US)|
|Number of pages||7|
|Journal||Journal of Immunology|
|State||Published - Jan 1 1980|
ASJC Scopus subject areas
- Immunology and Allergy