Mechanism of Helicobacter pylori-associated gastric mucosal injury.
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 of Helicobacter 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 the in vitro cytotoxic effects of ammonium chloride, sodium hypochlorite, monochloramine, and activated neutrophils on the target cells. Cytotoxicity was measured by a 51Cr-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 in Helicobacter pylori-associated gastric damage.
Dekigai
H
H
Department of Geriatric Medicine, Faculty of Medicine, Kyoto University, Japan.
Murakami
M
M
Kita
T
T
D000818:Animals; D002417:Cattle; D002478:Cells, Cultured; D003601:Cytotoxicity Tests, Immunologic / Q000379:methods; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects; D005753:Gastric Mucosa / Q000187:drug effects / Q000378:metabolism* / Q000382:microbiology; D016481:Helicobacter Infections / Q000209:etiology* / Q000378:metabolism / Q000382:microbiology; D016480:Helicobacter pylori / Q000302:isolation & purification / Q000378:metabolism / Q000472:pathogenicity*; D006801:Humans; D009504:Neutrophils / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D011651:Pulmonary Artery / Q000166:cytology / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D013272:Stomach Diseases / Q000209:etiology* / Q000378:metabolism / Q000382:microbiology; D013997:Time Factors