Myeloperoxidase-mediated platelet release reaction

Robert A Clark, S. J. Klebanoff

Research output: Contribution to journalArticle

27 Citations (Scopus)

Abstract

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, [3H]serotonin, and a cytoplasmic marker, [14C]adenine. Incubation of platelets with H2O2 alone (20 μM H2O2 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 H2O2 concentrations (>0.1 mM) or prolonged incubation (1-2 h). Serotonin release by H2O2 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 H2O2 concentrations as low as 10 μM. It was blocked by agents which inhibit peroxidase (azide, cyanide), degrade H2O2 (catalase), chelate Mg2+ (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, H2O2) are secreted by activated neutrophils, the reactions described here may have implications for neutrophil-platelet interaction in sites of thrombus formation.

Original languageEnglish (US)
Pages (from-to)177-183
Number of pages7
JournalJournal of Clinical Investigation
Volume63
Issue number2
StatePublished - 1979
Externally publishedYes

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Peroxidase
Blood Platelets
Serotonin
Adenine
Neutrophils
Dinitrophenols
Azides
Egtazic Acid
Deoxyglucose
Cyanides
Edetic Acid
Catalase
Hydrogen Peroxide
Thrombosis

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Myeloperoxidase-mediated platelet release reaction. / Clark, Robert A; Klebanoff, S. J.

In: Journal of Clinical Investigation, Vol. 63, No. 2, 1979, p. 177-183.

Research output: Contribution to journalArticle

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