Role of neutrophil-endothelial cell interactions in gastric mucosal injury induced by aspirin.
Recent studies have indicated that aspirin promotes neutrophil adherence to endothelium via CD11/CD18-dependent interactions with intercellular adhesion molecule 1, which subsequently leads to neutrophil-mediated cell injury. The objectives of the present study were to determine the role of neutrophil-endothelial cell interactions and lipid peroxidation in aspirin-induced gastric mucosal injury in rats. Oral administration of aspirin and HCl produced hemorrhagic erosions in the stomach of rats. Myeloperoxidase (MPO) activity in the gastric mucosa, an index of neutrophil infiltration, significantly increased 3 h after aspirin administration. The concentration of thiobarbituric acid-reactive substances (TBA-RS) in the gastric mucosa, an index of lipid peroxidation, increased slightly 3 h after aspirin administration. In rats treated with antineutrophil serum, both the total area of gastric erosions and MPO activity were significantly reduced. In addition, pretreatment with anti-CD18 monoclonal antibodies significantly attenuated gastric mucosal damage and inhibited the increases in both MPO activity and TBA-RS in the gastric mucosa after aspirin administration. These observations suggest that CD18-dependent neutrophil-endothelial cell interactions and lipid peroxidation play an important role in the pathogenesis of gastric mucosal lesions induced by aspirin.
Yoshida
N
N
First Department of Medicine, Kyoto Prefectural University of Medicine, Japan.
Yoshikawa
T
T
Nakamura
Y
Y
Arai
M
M
Matsuyama
K
K
Iinuma
S
S
Nishimura
S
S
Kondo
M
M
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000633:toxicity*; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D001241:Aspirin / Q000633:toxicity*; D002448:Cell Adhesion / Q000187:drug effects; D004727:Endothelium / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D005753:Gastric Mucosa / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D008297:Male; D009504:Neutrophils / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D009195:Peroxidase / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism*
D000894:Anti-Inflammatory Agents, Non-Steroidal; D000911:Antibodies, Monoclonal; D017392:Thiobarbituric Acid Reactive Substances; D009195:Peroxidase; D001241:Aspirin