Hemorrhage activates nf- b in murine lung mononuclear cells in
vivo.
Shenkar, Robert, Michael D. Schwartz, Lance S. Terada, John E. Repine,
Joe McCord, and Edward Abraham.
Division of Pulmonary Sciences and Critical Care Medicine,
University of Colorado Health Sciences Center, Denver, CO 80262 and
Webb-Waring Institute for Biomedical Research, Denver, CO 80262
APStracts 2:0231L, 1995.
Hemorrhage rapidly increases the expression of proinflammatory and
immunoregulatory cytokines in the lungs. Binding elements for the
nuclear transcriptional regulatory factors NF-_B and NF-IL6
(C/EBP[beta]) are present in the promoter regions of multiple
cytokine genes, including those whose expression is increased after
blood loss. In the present experiments, we found increased activation
in vivo of NF-_B in lung mononuclear cells, but not splenocytes,
taken from mice 1 hour after hemorrhage. In contrast, hemorrhage did
not activate NF-IL6 in lung cells or splenocytes. Inhibition of
xanthine oxidase by prior feeding of a tungsten-enriched diet
prevented hemorrhage-induced activation in lung cells of NF-_B.
Incubating splenocytes in vitro with xanthine oxidase activated NF
-_B, but not NF-IL6. Xanthine oxidase induced activation of NF-_B was
inhibited by manganese superoxide dismutase, but not catalase. These
results suggest that xanthine oxidase mediated, superoxide anion
dependent activation of NF-_B occurs in vivo and in vitro. This
mechanism may contribute to increased lung cytokine responses after
hemorrhage.
Received 3 April 1995; accepted in final form 4 December 1995.
APS Manuscript Number L103-5.
Article publication pending Am. J. Physiol. (Lung Cell. Mol.
Physiology).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 23 December 95