EFFECT OF MONOCHLORAMINE ON NEUTROPHIL-MEDIATED GASTRIC VASCULAR DAMAGE IN CULTURED ENDOTHELIAL-CELLS

Objective: Recently, we reported that ammonia produced by Helicobacter pylori damages the gastric mucosa. The gastric mucosal circulation is important in protecting gastric mucosa against aggressive forces. To investigate the pathophysiological mechanism by which ammonia damages gastric mucosa, we examined the effects of ammonia on the microcircula tory system. Design: H. pylori is associated with gastric mucosal dama ge and the infiltration of neutrophils. Myeloperoxidase from neutrophi ls produces hypochlorous acid which, in the presence of ammonia, yield s monochloramine. We therefore tested the hypothesis that ammonia, hyp ochlorous acid and monochloramine damage endothelial cells. Methods: W e studied the in vitro cytotoxic effects of ammonium chloride, sodium hypochlorite, monochloramine, and phorbol myristate acetate-stimulated polymorphonuclear neutrophils on cultured endothelial cells. Cytotoxi city was measured by a [Cr-51]-release assay. Results: Ammonium chlori de, 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 much-greater-than a mmonium chloride. Incubation of endothelial cells with phorbol myrista te acetate-stimulated polymorphonuclear neutrophils, H. pylori and ure a resulted in cytolysis. Conclusions: Monochloramine is more toxic to endothelial cells than ammonium chloride. It appears that ammonia, whi ch is produced by urease from H. pylori, is damaging to the gastric mi crocirculation through a reaction that forms monochloramine, and plays a part in H. pylori-associated gastric mucosal damage.