Eosinophil peroxidase-dependent hydroxyl radical generation by human eosinophils

Michael L. McCormick, Tedmund L. Roeder, Michelle A. Railsback, Bradley E Britigan

Research output: Contribution to journalArticle

43 Citations (Scopus)

Abstract

Eosinophil production of superoxide (O2/-·) and hydrogen peroxide (H2O2) is important in host defense. The present study assessed the potential of eosinophils to generate another potent cytotoxic species, the hydroxyl radical (·OH). ·OH formation by phorbol myristate acetate (PMA)- stimulated eosinophils was demonstrated using an α-(4-pyridyl-1-oxide)-N- tert-butyl nitrone/ethanol spin trapping system. Additionally, ·OH was spin trapped following the addition of purified eosinophil peroxidase (EPO) to a cell-free O2/-·/H2O2 generating systems. Effects of superoxide dismutase, catalase, azide, aminotriazole, chloride-depleted buffer, and extensive metal chelation were consistent with ·OH formation via the reaction of O2/-· and EPO-generated hypohalous acid. Under chloride- depleted conditions, physiologic concentrations of Br- increased ·OH formation by both PMA-stimulated eosinophils and the cell-free EPO system. Physiologic concentrations of SCN-, however, did not increase ·OH formation, and in the presence of both Br- and SCN-, ·OH formation was similar to SCN- only. Eosinophils appear to form ·OH via an EPO-dependent mechanism, the magnitude of which varies with the availability of various EPO substrates. Given the highly reactive nature of this radical and the ability of EPO to adhere to cell membranes, even small amounts of ·OH formed at such sites could contribute to eosinophil-mediated cytotoxicity.

Original languageEnglish (US)
Pages (from-to)27914-27919
Number of pages6
JournalJournal of Biological Chemistry
Volume269
Issue number45
StatePublished - Nov 11 1994

Fingerprint

Eosinophil Peroxidase
Eosinophils
Hydroxyl Radical
Tetradecanoylphorbol Acetate
Chlorides
Amitrole
Spin Trapping
Azides
Cell membranes
Cytotoxicity
Chelation
Superoxides
Catalase
Oxides
Hydrogen Peroxide
Superoxide Dismutase
Buffers
Ethanol
Metals
Cell Membrane

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Eosinophil peroxidase-dependent hydroxyl radical generation by human eosinophils. / McCormick, Michael L.; Roeder, Tedmund L.; Railsback, Michelle A.; Britigan, Bradley E.

In: Journal of Biological Chemistry, Vol. 269, No. 45, 11.11.1994, p. 27914-27919.

Research output: Contribution to journalArticle

McCormick, ML, Roeder, TL, Railsback, MA & Britigan, BE 1994, 'Eosinophil peroxidase-dependent hydroxyl radical generation by human eosinophils', Journal of Biological Chemistry, vol. 269, no. 45, pp. 27914-27919.
McCormick, Michael L. ; Roeder, Tedmund L. ; Railsback, Michelle A. ; Britigan, Bradley E. / Eosinophil peroxidase-dependent hydroxyl radical generation by human eosinophils. In: Journal of Biological Chemistry. 1994 ; Vol. 269, No. 45. pp. 27914-27919.
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