Interferon-gamma primes neutrophil-mediated gastric surface cell cytotoxicity. Lieser, Mark J., M. D., Robert A. Kozol, M. D., Steven D. Tennenberg, M. D. With The Technical Assistance Of Debra E. Fey, B. S., Rosemarie Czanko, B. S. and Jeffrey J. Weller, B. S. Department of Surgery, Allen Park Veterans Affairs Medical Center, Wayne State University School of Medicine, Detroit, Michigan.
APStracts 2:0007G, 1995.
The T-lymphocyte product interferon-gamma (IFN-g) upregulates or primes neutrophil (PMN) oxidative responses to the receptor-initiated stimulant fmet-leu-phe (FMLP) but not to the transduction-mediated stimulant phorbol myristate acetate (PMA). We sought a functional correlation between IFN-g -induced oxidative priming of PMNs and PMN-mediated cytotoxicity, using an in vitro assay of 51chromium release from rabbit gastric surface cells. Compared with control PMNs, IFN-g-primed PMNs exhibited a significant increase in cytotoxicity when stimulated with FMLP but not with PMA. IFN-g-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 hypochlorous acid 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-g primes the FMLP-stimulated cytotoxic activity of PMNs via the increased generation of reactive oxygen metabolites and that cytotoxicity may require effector-target cell adherence. Therefore, T-lymphocyte-derived IFN-g may have a role in the pathogenesis of PMN -mediated injury to gastric and gastrointestinal tract mucosa. Neutrophil (PMN) oxidative priming is defined as upregulation of PMN oxidative responses which occurs following exposure to a proinflammatory mediator. Priming of PMN responses is believed to play a significant role in host -defense and in the pathogenesis of tissue injury associated with the adult respiratory distress syndrome (ARDS), multiple system organ failure and ischemia/reperfusion (17,34,53). 

Received 25 January 1993; accepted in final form 3 January 1995.
APS Manuscript Number G0024-3.
Article publication pending Am. J. Physiol. (Gastrointest. Liver Physiology).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 23 February 1995.