Abstract
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.
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Yoshida N, Takemura T, Granger DN, Anderson DC, Wolf RE, McIntire LV, Kvietys PR: Molecular determinants of aspirin-induced neutrophil adherence to endothelial cells. Gastroenterology 105:715–724, 1993
Asako H, Kubes P, Wallace J, Wolf RE, Granger DN: Modulation of leukocyte adhesion in rat mesenteric venules by aspirin and salicylate. Gastroenterology 103:146–152, 1992
Asako H, Kubes P, Wallace J, Gaginella T, Wolf RE, Granger DN: Indomethacin-induced leukocyte adhesion in mesenteric venules: Role of lipoxygenase products. Am J Physiol 262:G903-G908, 1992
Wallace JL, Keenan CM, Granger DN: Gastric ulceration induced by non-steroidal anti-inflammatory drugs in a neutrophil dependent process. Am J Physiol 259:G462-G467, 1990
Yoshida N, Yoshikawa T, Nakamura Y, Arai M, Matuyama K, Iinuma S, Nishimura S, Kondo M: Role of neutrophilendothelial interactions in gastric mucosal injury induced by aspirin. J Clin Gastroenterol 1995 (in press)
Wallace JL, Arfors K-E, McKnight GW: A monoclonal antibody against the CD18 leukocyte adhesion molecule prevents indomethacin-induced gastric damage in the rat. Gastroenterology 100:878–883, 1991
Tonnesen MG: Neutrophil-endothelial cell interactions: Mechanisms of neutrophil adherence to vascular endothelium. J Invest Dermatol 93:53S-58S, 1989
Springer TA: Adhesion receptors of the immune system. Nature 346:425–434, 1990
Smith CW, Marlin SD, Rothlein R, Toman C, Anderson DC: Cooperative interactions of LFA-1 and Mac-1 with intercellular adhesion molecule-1 in facilitating adherence and transendothelial migration of human neutrophilsin vivo. J Clin Invest 83:2008–2017, 1989
Ito M, Guth PH: Role of oxygen-derived free radicals in hemorrhagic shock-induced gastric lesions in the rat. Gastroenterology 88:1162–1167, 1985
Perry MA, Wadhwa S, Parks DA, Pickard W, Granger DN: Role of oxygen radicals in ischemia-induced lesions in the cat stomach. Gastroenterology 90:362–367, 1986
Yoshikawa T, Yoshida N, Miyagawa H, Takemura T, Tanigawa T, Sugino S, Kondo M: Role of lipid peroxidation in gastric mucosal lesions induced by burn shock in rats. J Clin Biochem Nutr 2:163–170, 1987
Yoshida N, Yoshikawa T, Ando T, Naito Y, Oyamada H, Takemura T, Tanigawa T, Sugino S, Kondo M: Pathogenesis of platelet-activating factor induced gastric mucosal damage in rats. Scand J Gastroenterol 24:210–214, 1989
Yoshikawa T, Naito Y, Kishi A, Tomii T, Kaneko T, Iinuma S, Ichikawa H, Yasuda M, Takahashi S, Kondo M: Role of active oxygen, lipid peroxidation, and antioxidants in the pathogenesis of gastric mucosal injury induced by indomethacin in rats. Gut 34:732–737, 1993
Yoshikawa T, Ueda S, Naito Y, Takahashi S, Oyamada H, Morita Y, Yoneda T, Kondo M: Role of oxygen-derived free radicals in gastric mucosal injury induced by ischemia or ischemia-reperfusion in rats. Free Rad Res Comms 7:3–6, 1989
Babior BM, Kipnes RS, Curnutee JT: Biological defense mechanism. The production by leukocytes of superoxide, a potential bactericidal agent. J Clin Invest 52:741–744, 1973
Tamatani T, Kotani M, Miyasaka M: Characterization of the rat leukocyte integrin, CD11/CD18, by the use of LFA-1 subunit-specific monoclonal antibodies. Eur J Immunol 21:627–633, 1991
Tamatani T, Miyasaka M: Identification of monoclonal antibodies reactive with the rat homolog of ICAM-1, and evidence for a differential involvement of ICAM-1 in the adherence of resting versus activated lymphocytes to high endothelial cells. Int Immunol 2:165–171, 1990
Krawisz JE, Sharon P, Stenson WF: Quantitative assay for acute intestinal inflammation based on myeloperoxidase activity. Gastroenterology 87:1344–1350, 1984
Miyagawa H, Yoshikawa T, Tanigawa T, Yoshida N, Sugino S, Kondo M: Measurement of serum superoxide dismutase activity by electron spin resonance. J Clin Biochem Nutr 5:1–7, 1988
Carlos TM, Harlan JM: Membrane proteins involved in phagocyte adherence to endothelium. Immunol Rev 114:5–28, 1990
Wallace JL, McKnight W, Miyasaka M, Tamatani T, Paulson J, Anderson DC, Granger DN, Kubes P: Role of endothelial adhesion molecules in NSAID-induced gastric mucosal injury. Am J Physiol 265:G993-G998, 1993
Tappel AL: Lipid peroxidation damage to cell components. Fed Proc 32:1870–1874, 1973
Smith SM, Holm-Rutili L, Perry MA, Grisham MB, Arfors KE, Granger DN, Kvietys PR: Role of neutrophils in hemorrhagic shock-induced gastric mucosal injury in the rat. Gastroenterology 98:466–471, 1987
Suzuki M, Inauen W, Kvietys PR, Grisham MB, Meininger C, Schelling ME, Granger HJ, Granger DN: Superoxide mediates reperfusion-induced leukocyte-endothelial interactions. Am J Physiol 257:H1740-H1745, 1989
Yoshida N, Granger DN, Anderson DC, Rothlein R, Lane C, Kvietys PR: Anoxia/reoxygenation-induced neutrophil adherence to cultured endothelial cells. Am J Physiol 262:H1891-H1898, 1992
Nakamura Y, Yoshida N, Yoshikawa T, Arai M, Matsuyama K, Kondo M: Hydrogen peroxide-induced neutrophil endothelial cell interactions.In Frontiers of Reactive Oxygen Species in Biology and Medicine. K Asada, T Yoshikawa (eds). Amsterdam, Excerpta Medica, 1994, pp 227–228
Inauen W, Granger DN, Meininger CJ, Schelling ME, Granger HJ, Kvietys PR: Anoxia-reoxygenation-induced, neutrophilmediated endothelial cell injury: Role of elastase. Am J Physiol 259:H925-H931, 1990
Yoshida N, Cepinskas G, Granger DN, Anderson DC, Wolf RE, Kvietys PR: Aspirin-induced, neutrophil-mediated injury to vascular endothelium. (submitted)
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Yoshida, N., Yoshikawa, T., Nakamura, Y. et al. Role of neutrophil-mediated inflammation in aspirin-induced gastric mucosal injury. Digest Dis Sci 40, 2300–2304 (1995). https://doi.org/10.1007/BF02063228
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DOI: https://doi.org/10.1007/BF02063228