ROLE OF NEUTROPHIL-MEDIATED INFLAMMATION IN ASPIRIN-INDUCED GASTRIC-MUCOSAL INJURY

The objectives of this study were to determine the roles of neutrophil -endothelial cell interactions and oxygen-derived free radicals in the pathogenesis of aspirin-induced gastric mucosal injury in rats. Oral administration of acidified aspirin (200 mg/kg) resulted in linear hem orrhagic erosions and an increase in myeloperoxidase activity, an inde x of neutrophil infiltration, in the gastric mucosa. Aspirin-induced g astric damage and the increase in myeloperoxidase activity were signif icantly inhibited by the injection of anti-CD11a, anti-CD11b, anti-int ercellular adhesion molecule-1 monoclonal antibodies, and the combinat ion of superoxide dismutase and catalase, which are scavengers of acti ve oxygen species. These results suggest that neutrophil-endothelial a dhesive interactions, which occur via CD11a/CD18- and CD11b/CD18-depen dent interactions with intercellular adhesion molecule-1, and oxygen-d erived free radicals produced by neutrophils are implicated in the pro duction of aspirin-induced gastric mucosal injury.