Mechanism ofhelicobacter pylori-associated gastric mucosal injury
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Helicobacter pylori infection is associated with gastric mucosal damage and the infiltration of neutrophils. Myeloperoxidase from neutrophils produces hypochlorous acid, which yields monochloramine in the presence of ammonia produced by urease enzyme ofHelicobacter pylori. The target cells of gastric mucosal damage are gastric mucosal cells and endothelial cells. We therefore tested the hypothesis that ammonium, hypochlorous acid, and monochloramine damage the target cells. We studied thein vitro cytotoxic effects of ammonium chloride, sodium hypochlorite, monochloramine, and activated neutrophils on the target cells. Cytotoxicity was measured by a51Cr-release assay. Ammonium chloride, sodium 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>>ammonium chloride. Incubation of labeled cells with activated neutrophils,Helicobacter pylori, and urea resulted in cytolysis. These cytotoxicities were significantly inhibited by the scavenger of hypochlorous acid, taurine. Monochloramine is more toxic to the target cells than ammonium chloride. Although ammonium chloride at neutral pH by itself has little direct damaging effect on the gastric mucosa, it is damaging to the gastric mucosa through a reaction with hypochlorous acid, suggesting that it plays a role inHelicobacter pylori-associated gastric damage.
Key wordsHelicobacter pylori ammonia monochloramine neutrophils gastric mucosa
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