Role of neutrophil-mediated inflammation in aspirin-induced gastric mucosal injury.
The objectives of this study were to determine the roles of neutrophil-endothelial cell interactions and oxygen-derived free radicals in the pathogenesis of aspirin-induced gastric mucosal injury in rats. Oral administration of acidified aspirin (200 mg/kg) resulted in linear hemorrhagic erosions and an increase in myeloperoxidase activity, an index of neutrophil infiltration, in the gastric mucosa. Aspirin-induced gastric damage and the increase in myeloperoxidase activity were significantly inhibited by the injection of anti-CD11a, anti-CD11b, anti-intercellular adhesion molecule-1 monoclonal antibodies, and the combination of superoxide dismutase and catalase, which are scavengers of active oxygen species. These results suggest that neutrophil-endothelial adhesive interactions, which occur via CD11a/ CD18- and CD11b/CD18-dependent interactions with intercellular adhesion molecule-1, and oxygen-derived free radicals produced by neutrophils are implicated in the production of aspirin-induced gastric mucosal injury.
Yoshida
N
N
First Department of Internal Medicine, Kyoto Prefectural University of Medicine, Japan.
Yoshikawa
T
T
Nakamura
Y
Y
Arai
M
M
Matsuyama
K
K
Iinuma
S
S
Yagi
N
N
Naito
Y
Y
Miyasaka
M
M
Kondo
M
M
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000633:toxicity*; D000911:Antibodies, Monoclonal; D001241:Aspirin / Q000633:toxicity*; D018845:CD11 Antigens / Q000276:immunology / Q000502:physiology; D002374:Catalase / Q000494:pharmacology; D005609:Free Radicals / Q000378:metabolism; D005753:Gastric Mucosa / Q000187:drug effects* / Q000201:enzymology / Q000473:pathology; D005756:Gastritis / Q000139:chemically induced / Q000473:pathology / Q000503:physiopathology; D018799:Intercellular Adhesion Molecule-1 / Q000276:immunology / Q000502:physiology; D008297:Male; D009504:Neutrophils / Q000502:physiology*; D009195:Peroxidase / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013482:Superoxide Dismutase / Q000494:pharmacology
D000894:Anti-Inflammatory Agents, Non-Steroidal; D000911:Antibodies, Monoclonal; D018845:CD11 Antigens; D005609:Free Radicals; D018799:Intercellular Adhesion Molecule-1; D002374:Catalase; D009195:Peroxidase; D013482:Superoxide Dismutase; D001241:Aspirin