Interferon-γ primes neutrophil-mediated gastric surface cell cytotoxicity

M. J. Lieser, R. A. Kozol, S. D. Tennenberg

Research output: Contribution to journalArticle

11 Scopus citations

Abstract

The T lymphocyte product interferon-γ (IFN-γ) upregulates or primes polymorphonuclear leukocyte (PMN) oxidative responses to the receptor- initiated stimulant N-formyl-methionyl-leucyl-phenylalanine (FMLP) but not to the transduction-mediated stimulant phorbol myristate acetate (PMA). We sought a functional correlation between IFN-γ-induced oxidative priming of PMNs and PMN-mediated cytotoxicity, using an in vitro assay of 51Cr release from rabbit gastric surface cells. Compared with control PMNs, IFN-γ-primed PMNs exhibited a significant increase in cytotoxicity when stimulated with FMLP, but not when stimulated with PMA. IFN-γ-induced, FMLP-stimulated, PMN- mediated cytotoxicity was reduced by adding superoxide dismutase to scavenge superoxide anion or by adding catalase or glutathione peroxidase to scavenge hydrogen peroxide. Cytotoxicity was also reduced by inhibiting myeloperoxidase activity with azide or scavenging HOCl with alanine or methionine. Cytotoxicity was blocked by a monoclonal antibody against the CD11/CD18 integrin of PMNs. The results indicate that the immunoregulatory lymphokine IFN-γ primes the FMLP-stimulated cytotoxic activity of PMNs via the increased generation of reactive oxygen metabolites and indicate that cytotoxicity may require effector-target cell adherence. Therefore, T lymphocyte-derived IFN-γ may have a role in the pathogenesis of PMN-mediated injury to gastric and gastrointestinal tract mucosa.

Original languageEnglish (US)
Pages (from-to)G843-G848
JournalAmerican Journal of Physiology - Gastrointestinal and Liver Physiology
Volume268
Issue number5 31-5
DOIs
StatePublished - 1995

Keywords

  • CD18
  • hydrogen peroxide
  • hypochlorous acid
  • inflammation
  • N-formyl-methionyl-leucyl-phenylalanine
  • phorbol myristate acetate
  • reactive oxygen metabolites
  • superoxide

ASJC Scopus subject areas

  • Physiology
  • Gastroenterology
  • Agricultural and Biological Sciences(all)

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