Neutrophil accumulation in development gastric ulcer induced by submucosal injection of endothelin-1 in rats.
Submucosal injection of endothelin (ET)-1 induces gastric ulcer. We investigated the roles of neutrophils and adhesion molecules (intercellular adhesion molecule (ICAM)-1 and CD18) in the development of ET-1-induced ulcers in rats. Ulcers were induced by submucosal injection of ET-1. Rats were injected with anti-neutrophil serum or F(ab')2 fragments of irrelevant mouse IgG2a (control), anti-ICAM-1 antibody, or anti-CD18 antibody. Ulcer tissues were subjected to measurement of myeloperoxidase (MPO) activity, ulcer size, and immunohistochemical study. Within 3 hr, arterial vasoconstriction and vascular congestion were observed at sites of ET-1 injection. By 6 hr, vascular congestion had disappeared, and ICAM-1 expression had markedly increased in venules in deep portions of the mucosa and submucosa, accompanied by an increase in the number of CD18-positive neutrophils. By 48 hr, ulcers that extended into the submucosa had developed. In controls, MPO activity gradually increased and was maximal by 6 hr. Neutrophil depletion, and immunoneutralizing of ICAM-1 and CD18 inhibited the increase in MPO activity, and decreased ulcer sizes measured at 48 hr. In conclusion, ET-1 causes ischemia-reperfusion injury, and neutrophil accumulation after reperfusion mediated by the ICAM-1-CD18 pathway may be important in the development of ET-1-induced gastric ulcer.
Watanabe
T
T
Department of Biosignal Analysis, Osaka City University Medical School, Osaka, Japan.
Arakawa
T
T
Tominaga
K
K
Fujiwara
Y
Y
Higuchi
K
K
Kuroki
T
T
D000818:Animals; D018821:CD18 Antigens / Q000502:physiology; D019332:Endothelin-1 / Q000008:administration & dosage / Q000502:physiology*; D005753:Gastric Mucosa / Q000098:blood supply / Q000276:immunology / Q000473:pathology; D007267:Injections; D018799:Intercellular Adhesion Molecule-1 / Q000502:physiology; D008297:Male; D051379:Mice; D009504:Neutrophils / Q000276:immunology* / Q000473:pathology; D009195:Peroxidase / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D015427:Reperfusion Injury / Q000276:immunology / Q000473:pathology; D013276:Stomach Ulcer / Q000276:immunology* / Q000473:pathology
D018821:CD18 Antigens; D019332:Endothelin-1; D018799:Intercellular Adhesion Molecule-1; D009195:Peroxidase