Neutrophil accumulation in development of gastric ulcer induced by submucosal injection of endothelin-1 in rats

• Published in: Digestive diseases and sciences 2000-05, Vol.45 (5), p.880-888
• Main Authors: WATANABE, T, ARAKAWA, T, TOMINAGA, K, FUJIWARA, Y, HIGUCHI, K, KUROKI, T
• Format: Article
• Language: English
• Subjects: Animals; Biological and medical sciences; CD18 Antigens - physiology; Endothelin-1 - administration & dosage; Endothelin-1 - physiology; Gastric Mucosa - blood supply; Gastric Mucosa - immunology; Gastric Mucosa - pathology; Gastroenterology. Liver. Pancreas. Abdomen; Injections; Intercellular Adhesion Molecule-1 - physiology; Male; Medical sciences; Mice; Neutrophils - immunology; Neutrophils - pathology; Peroxidase - metabolism; Rats; Rats, Wistar; Reperfusion Injury - immunology; Reperfusion Injury - pathology; Stomach Ulcer - immunology; Stomach Ulcer - pathology; Stomach. Duodenum. Small intestine. Colon. Rectum. Anus; Tumors
• ISSN: 0163-2116; 1573-2568
• DOI: 10.1023/a:1005556520813

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.