EFFECT OF CIGARETTE-SMOKE ON ETHANOL-INDUCED GASTRIC-MUCOSAL LESIONS - THE ROLE OF NITRIC-OXIDE AND NEUTROPHILS

The roles of neutrophil aggregation, inducible nitric oxide synthase a ctivation and chemoattractant, leukotriene B-4, in potentiation of the cigarette smoke effect on ethanol-induced gastric mucosal damage were studied. Smoke exposure markedly increased gastric lesion formation f ollowing ethanol administration and this was accompanied by substantia l increase in gastric mucosal leukotriene B-4 concentration, myelopero xidase and inducible nitric oxide synthase activities. Antineutrophil serum or aminoguanidine pretreatment significantly attenuated both gas tric mucosal lesion formation and inducible nitric oxide synthase acti vity. The increased myeloperoxidase activity was abolished by antineut rophil serum but not by aminoguanidine. These data indicated that both neutrophil mobilization and inducible nitric oxide synthase activatio n in the gastric mucosa play an important role in the potentiating act ion of cigarette smoke on ethanol-induced gastric mucosal lesion forma tion. Increased synthesis of nitric oxide fr om inducible nitric oxide synthase during gastric damage may be secondary to neutrophil infiltr ation in the gastric mucosa. Chemoattractant leukotriene B-4 could als o contribute to neutrophil recruitment in the tissue. (C) 1998 Elsevie r Science B.V.