Chemotactic factor inactivation by the myeloperoxidase-hydrogen peroxide-halide system. An inflammatory control mechanism

R. A. Clark, S. J. Klebanoff

Research output: Contribution to journalArticlepeer-review

81 Scopus citations

Abstract

Polymorphonuclear leukocytes may modulate the acute inflammatory response by the secretion of enzymes capable of inactivating mediators of inflammation. The ability of the myeloperoxidase-H2O2-halide system of the neutrophil to inactivate chemoattractants was examined using both a radioassay and a morphologic assay of chemotaxis. Incubation of either a complement-derived agent, C5a, or a synthetic formyl-methionyl peptide chemoattractant with the myeloperoxidase system for 15 min at 37°C resulted in essentially complete loss of chemotactic activity. Inactivation was dependent on enzymatically active myeloperoxidase, H2O2 or a peroxide-generating enzyme system, and a halide cofactor. It was blocked by agents which inhibit peroxidase (azide) or degrade H2O2 (catalase). Inactivation of chemoattractants was time-dependent, reaching maximal levels within 1-5 min, and temperature-dependent with no significant inactivation occurring at 0°C. H2O2 alone had no significant inactivating ability of concentrations as high as 10 mM, whereas in the presence of myeloperoxidase and a halide, 0.1 μM, H2O2 showed significant activity and 10 μM H2O2 caused complete inactivation. On a molar basis, the order of effectiveness of the halide cofactors was Br- > I- > Cl-, although only chloride was fully active at physiologic concentrations. Neutrophils stimulated by phagocytosis or by membrane-perturbing agents secrete enzymatic constituents, including myeloperoxidase, and metabolic products such as H2O2. Thus, it is suggested that the myeloperoxidase system acting at an extracellular site serves as an inflammatory control mechanism by virtue of its ability to inactivate neutrophil chemoattractants.

Original languageEnglish (US)
Pages (from-to)913-920
Number of pages8
JournalJournal of Clinical Investigation
Volume64
Issue number4
DOIs
StatePublished - 1979
Externally publishedYes

ASJC Scopus subject areas

  • Medicine(all)

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