Leukotriene B4 promotes reactive oxidant generation and leukocyte adherence
during acute hypoxia.
Steiner, Dawn R. S., Norberto C. Gonzalez, and John G. Wood.
Department of Molecular and Integrative Physiology, University of Kansas Medical
Center, Kansas City, Kansas 66160
APStracts 8:0302A, 2001.
Acute systemic hypoxia produces rapid leukocyte adherence in the rat mesenteric
microcirculation, although the underlying mechanisms are not fully known. Hypoxia is
known to increase reactive oxidant species (ROS) generation, which could result in
formation of the lipid inflammatory mediator leukotriene B4 (LTB4). The goal of this
study was to examine the role of LTB4 in hypoxia-induced microvascular alterations.
Using intravital microscopy, we determined the effect of the LTB4 antagonist, LTB4-
dimethyl amide (LTB4-DMA), on ROS generation and leukocyte adherence in
mesenteric venules during hypoxia. Exogenous LTB4 increased ROS generation to 144 ±
8% compared with control values and also promoted leukocyte adherence. These
responses to LTB4 were blocked by pretreating the mesentery with LTB4-DMA.
Leukopenia did not significantly attenuate the LTB4-induced increase in ROS generation
(142 ± 12.1%). LTB4-DMA substantially, though not completely, reduced hypoxia-
induced ROS generation from 66 ± 18% to 11 ± 4% above control values. Hypoxia-
induced leukocyte adherence was significantly attenuated by LTB4-DMA. Our results
support a role for LTB4 in the mechanism of hypoxia-induced ROS generation and
leukocyte adherence in the rat mesenteric microcirculation.
Received 14 February 2001; accepted in final form 15 May 2001
APS Manuscript Number A0155-1.
Article publication pending J Appl Physiol
ISSN 1080-4757 Copyright 2001 The American Physiological Society.
Published in APStracts on 18 June 2001