APStracts 3:0003H, 1996.

Hydrogen peroxide induces leukocyte rolling: modulation by endogenous antioxidant mechanisms including nitric oxide. Johnston, Brent, Samina Kanwar, and Paul Kubes. Department of Medical Physiology, Immunology Research Group, University of Calgary, Calgary, Alberta, T2N 4N1

APStracts 3:0003H, 1996.

In this study, intravital microscopy was used to examine the mechanisms which regulate hydrogen peroxide (H2O2)-induced leukocyte rolling within rat mesenteric venules in vivo. H2O2 elicited leukocyte rolling within a narrow response window between 10 and 500 [mu]M H2O2. Continuous superfusion with 100 [mu]M H2O2 induced a large but transient increase in the flux of rolling leukocytes, while a short 5 min pulse elicited a sustained increase in rolling flux. Both treatments caused increases in leukocyte adhesion. H2O2-induced increases in leukocyte flux and adhesion could be prevented with an anti-P-selectin antibody. Inhibition of endogenous catalase (aminotriazole), glutathione (diethyl maleate), or nitric oxide (NG -nitro-L-arginine methyl ester) shifted the effective concentration of H2O2; continuous superfusion with 10 [mu]M H2O2 now elicited large and sustained increases in leukocyte rolling flux, while 100 [mu]M H2O2 elicited less than optimal responses. Dual antioxidant inhibition further reduced the effective H2O2 concentration to 1 [mu]M H2O2. A nitric oxide donor prevented the increased rolling flux induced by 100 [mu]M H2O2. These findings suggest that endogenous antioxidants are important regulators of H2O2-induced, P-selectin -dependent leukocyte rolling in vivo.

Received 21 August 1995; accepted in final form 14 December 1995.
APS Manuscript Number H788-5.
Article publication pending Am. J. Physiol. (Heart Circ. Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 22 January 96