Interferon-gamma primes neutrophil-mediated gastric surface cell cytotoxicity.
The T lymphocyte product interferon-gamma (IFN-gamma) 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-gamma-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-gamma-primed PMNs exhibited a significant increase in cytotoxicity when stimulated with FMLP, but not when stimulated with PMA. IFN-gamma-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-gamma 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-gamma may have a role in the pathogenesis of PMN-mediated injury to gastric and gastrointestinal tract mucosa.
Lieser
M J
MJ
Department of Surgery, Allen Park Veterans Affairs Medical Center, Detroit, Michigan, USA.
Kozol
R A
RA
Tennenberg
S D
SD
D000911:Antibodies, Monoclonal / Q000276:immunology; D018821:CD18 Antigens / Q000276:immunology; D003602:Cytotoxicity, Immunologic; D006801:Humans; D006997:Hypochlorous Acid / Q000378:metabolism; D007371:Interferon-gamma / Q000494:pharmacology*; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D009504:Neutrophils / Q000502:physiology*; D013270:Stomach / Q000166:cytology*
D000911:Antibodies, Monoclonal; D018821:CD18 Antigens; D009240:N-Formylmethionine Leucyl-Phenylalanine; D006997:Hypochlorous Acid; D007371:Interferon-gamma