MECHANISM OF HELICOBACTER-PYLORI-ASSOCIATED GASTRIC-MUCOSAL INJURY

Helicobacter pylori infection is associated with gastric mucosal damag e and the infiltration of neutrophils. Myeloperoxidase from neutrophil s produces hypochlorous acid, which yields monochloramine in the prese nce of ammonia produced by urease enzyme of Helicobacter pylori. The t arget cells of gastric mucosal damage are gastric mucosal cells and en dothelial cells. We therefore tested the hypothesis that ammonium, hyp ochlorous acid, and monochloramine damage the target cells. We studied the in vitro cytotoxic effects of ammonium chloride, sodium hypochlor ite, monochloramine, and activated neutrophils on the target cells. Cy totoxicity was measured by a Cr-51-release assay. Ammonium chloride, s odium hypochlorite, and monochloramine were toxic to labeled cells in a concentration dependent manner. The toxicity of these agents was in the order monochloramine > sodium hypochlorite much greater than ammon ium chloride. Incubation of labeled cells with activated neutrophils, Helicobacter pylori, and urea resulted in cytolysis. These cytotoxicit ies were significantly inhibited by the scavenger of hypochlorous acid , taurine. Monochloramine is more toxic to the target cells than ammon ium chloride. Although ammonium chloride at neutral pH by itself has l ittle direct damaging effect on the gastric mucosa, it is damaging to the gastric mucosa through a reaction with hypochlorous