Chemotactic factor inactivation by myeloperoxidase-mediated oxidation of methionine

R. A. Clark, S. Szot, K. Venkatasubramanian, E. Schiffmann

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44 Scopus citations


The myeloperoxidase-H2O2-halide system of the polymorphonuclear leukocyte is capable of inactivating certain leukoattractants, including complement-derived and synthetic peptide agents. The biochemical basis for this phenomenon was explored. The peroxidase system readily inactivated methionine-containing chemoatractants (C5a, f-met-leu-phe, f-met-leu-phe-lys), whereas agents not containing methionine (f-norleu-leu-phe, f-phe-leu-phe-leu-phe) were unaffected. Exposure of f-met-leu-phe to the myeloperoxidase system also resulted in a marked decrease in the binding of the peptide to specific neutrophil membrane receptors, but peroxidase treatment of f-Norleu-leu-phe had no effect on its receptor binding. The inactivation of f-met-leu-phe by the myeloperoxidase system was blocked by reducing agents (2-mercaptoethanol, ascorbic acid) and by free methionine, but not by methionine sulfoxide. Thin-layer chromatography of f-met-leu-[3H]phe demonstrated that peroxidase treatment resulted in a shift to a more slowly migrating species with an Rf value corresponding to that of the peptide containing chemically oxidized methionine. These results indicate that the inactivation of peptide chemoattractants by the myeloperoxidase system is a consequence of methionine oxidation and that this biochemical alteration decreases the affinity of the peptide for neutrophil membrane receptors. Since activated neutrophils secrete myeloperoxidase and H2O2, we suggest that the inactivation of inflammatory mediators by this enzyme system may constitute a control mechanism in the tissue response to injury. Other biologic mediators, especially those containing thioether groups, may also be affected by oxidants generated via the myeloperoxidase-catalyzed oxidation of halides by H2O2.

Original languageEnglish (US)
Pages (from-to)2020-2026
Number of pages7
JournalJournal of Immunology
Issue number4
StatePublished - Jan 1 1980
Externally publishedYes

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology


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