Reactive oxidants mediate tumor necrosis factor[alpha]-induced leukocyte adhesion to rat mesenteric venular endothelium. Morita, Yutaka, Mark G. Clemens, Lloyd S. Miller, Urvashi Rangan, Shinji Kondo, Masayuki Miyasaka, Toshikazu Yoshikawa, Gregory B. Bulkley. Department of Surgery, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21287-4685, Department of Bioregulation Biomedical Research Center, The Osaka University Medical School, Suita 565, Japan, First Department of Internal Medicine, Kyoto Prefectural University of Medicine, Kyoto 602, Japan
APStracts 2:0200H, 1995.
We investigated the role of reactive oxygen metabolites (ROMs) as potential mediators of tumor necrosis factor [alpha] (TNF[alpha]) -stimulated neutrophil adhesion to rat mesenteric venules in vivo, using intravital microscopy and fixed whole-mount preparations of mesentery. Intraperitoneal injection of TNF[alpha] significantly increased leukocyte rolling, adhesion and emigration in a dose and time dependent manner. This leukocyte adhesion and emigration, but not rolling, were significantly attenuated by prior intravenous administration of monoclonal anti-intercellular adhesion molecule-1 (ICAM-1). Rolling leukocyte flux was significantly attenuated by pre -administration of superoxide dismutase (SOD), catalase or both, each given intravenously. Only catalase or SOD + catalase significantly inhibited leukocyte adhesion. Catalase alone inhibited emigration. Moreover, post-adhesive treatment with catalase but not SOD, 4h after TNF[alpha] administration reduced the flux of rolling (but not adherent) leukocytes that had previously increased in response to TNF[alpha]. Intragastric allopurinol (50mg/kg at 3 and 18h before TNF[alpha] administration) or 3 weeks of a tungsten-enriched diet substantially inhibited xanthine oxidase activity but had no significant effects on the above parameters of neutrophil dynamics. In parallel experiments using fixed whole-mount preparations of the mesoappendix stained specifically for neutrophil esterase, neutrophil adhesion 2h after TNF[alpha] administration was also inhibited by continuous intravenous administration of catalase but not by SOD, intragastric allopurinol nor tungsten diet. These findings suggest that reactive oxygen metabolites, apparently not from xanthine oxidase, constitute important mediators of TNF[alpha]-induced upregulation of neutrophil adhesion in rat mesenteric venules. 

Received 9 December 1994; accepted in final form 12 May 1995.
APS Manuscript Number H1080-4.
Article publication pending Am. J. Physiol. (Heart Circ. Physiology).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 26 May 1995.