Il-1b stimulates early superoxide and delayed peroxynitrite
production by pulmonary vascular smooth muscle cells.
Boota, Ahmad, Harvey Zar, Young-Myeong Kim, Bruce Johnson, Bruce Pitt,
and Paul Davies.
Departments of Pulmonary, Allergy & Critical Care Medicine,
Anesthesiology, Surgery and Pharmacology, University of Pittsburgh
School of Medicine, Pittsburgh, PA 15261
APStracts 3:0127L, 1996.
Our previous studies have shown that rat pulmonary microvascular
smooth muscle cells (RPMSMC) upregulate inducible nitric oxide
synthase (iNOS) and produce nitric oxide (NO) when treated with IL
-1b. We now report that an additional effect of IL-1[beta] stimulation
in RPMSMC is an increase in production of superoxide (O2- ) that
results in the formation of peroxynitrite (ONOO-). IL-1[beta]
produced a rapid (within 1 hr), concentration-dependent increase in
O2- as detected by ferricytochrome C reduction and lucigenin-enhanced
chemiluminescence. Superoxide production was sensitive to quinacrine
and diphenyliodonium, suggesting that NADH and NADPH oxidoreductases
were responsible. Following induction of iNOS and production of iNOS
-derived NO, ONOO- was detected by luminol-enhanced chemiluminescence
and was found to cause lipid peroxidation and form nitrotyrosine in
the cytoskeleton, detected by immunostaining. Cell viability,
however, appeared unaffected. IL-1b-mediated induction of RPMSMC
-derived ONOO- may have significant effects on pulmonary vascular
function in sepsis and inflammatory states.
Received 28 March 1996; accepted in final form 8 July 1996.
APS Manuscript Number L104-6.
Article publication pending Am. J. Physiol. (Lung Cell. Mol.
Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 21 August 1996