Mechanisms and roles of neutrophil infiltration in stress-induced gastric injury in rats.
Water-immersion and restraint stress is associated with an increase in neutrophil infiltration into the gastric mucosa, but the mechanism responsible for this infiltration is unclear. We investigated the involvement of intercellular adhesion molecule-1 (ICAM-1) and tumor necrosis factor-alpha (TNF-alpha) in neutrophil infiltration in stress-induced gastric injury in rats. Rats were administered neutralizing antibody against ICAM-1 or TNF-alpha and were subjected to induction of gastric injury by 6-hr water-immersion and restraint stress. To evaluate the relationship between gastric acid and neutrophil infiltration, some rats were given cimetidine before administration of stress. Neutralizing antibodies inhibited both the lesion formation and the increase in myeloperoxidase activity induced by stress. Expression of ICAM-1 on endothelial cells was increased by stress, accompanied by an increase of TNF-alpha-positive cells. Antibody against TNF-alpha inhibited this increase in ICAM-1 expression. Cimetidine almost completely inhibited gastric lesions, but did not affect myeloperoxidase activity. In conclusion, neutrophil infiltration in stress-induced gastric injury may be mediated by ICAM-1 and TNF-alpha, but not gastric acid, and may play crucial roles in the progression of gastric injury.
Hamaguchi
M
M
Department of Gastroenterology, Osaka City University Medical School, Osaka, Japan.
Watanabe
T
T
Higuchi
K
K
Tominaga
K
K
Fujiwara
Y
Y
Arakawa
T
T
D000818:Animals; D000897:Anti-Ulcer Agents / Q000494:pharmacology; D002927:Cimetidine / Q000494:pharmacology; D005753:Gastric Mucosa / Q000473:pathology; D007101:Immersion; D007150:Immunohistochemistry; D018799:Intercellular Adhesion Molecule-1 / Q000276:immunology; D008297:Male; D020556:Neutrophil Infiltration / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D012149:Restraint, Physical; D013270:Stomach / Q000473:pathology*; D013312:Stress, Physiological / Q000503:physiopathology*; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology
D000897:Anti-Ulcer Agents; D014409:Tumor Necrosis Factor-alpha; D018799:Intercellular Adhesion Molecule-1; D002927:Cimetidine