AJP - Gastrointestinal and Liver Physiology, Vol 268, Issue 5 843-G848, Copyright © 1995 by American Physiological Society
Interferon-gamma primes neutrophil-mediated gastric surface cell cytotoxicity
M. J. Lieser, R. A. Kozol and S. D. Tennenberg
Department of Surgery, Allen Park Veterans Affairs Medical Center, Detroit, Michigan, USA.
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.
