Proinflammatory role of inducible nitric oxide synthase in acute hyperoxic lung injury.
BACKGROUND
Hyperoxic exposures are often found in clinical settings of respiratory insufficient patients, although oxygen therapy (>50% O2) can result in the development of acute hyperoxic lung injury within a few days. Upon hyperoxic exposure, the inducible nitric oxide synthase (iNOS) is activated by a variety of proinflammatory cytokines both in vitro and in vivo. In the present study, we used a murine hyperoxic model to evaluate the effects of iNOS deficiency on the inflammatory response.


METHODS
Wild-type and iNOS-deficient mice were exposed to normoxia, 60% O2 or >95% O2 for 72 h.


RESULTS
Exposure to >95% O2 resulted in an increased iNOS mRNA and protein expression in the lungs from wild-type mice. No significant effects of iNOS deficiency on cell differential in bronchoalveolar lavage fluid were observed. However, hyperoxia induced a significant increase in total cell count, protein concentration, LDH activity, lipid peroxidation, and TNF-alpha concentration in the bronchoalveolar lavage fluid compared to iNOS knockout mice. Moreover, binding activity of NF-kappaB and AP-1 appeared to be higher in wild-type than in iNOS-deficient mice.


CONCLUSIONS
Taken together, our results provide evidence to suggest that iNOS plays a proinflammatory role in acute hyperoxic lung injury.
Hesse
Anne-Karin
AK
Institute for Surgical Research, University of Munich, Marchioninistr, 15, 81366 Munich, Germany. ak.hesse@web.de <ak.hesse@web.de>
Dörger
Martina
M
Kupatt
Christian
C
Krombach
Fritz
F
D000208:Acute Disease; D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000276:immunology; D016207:Cytokines / Q000276:immunology; D018496:Hyperoxia / Q000201:enzymology*; D007155:Immunologic Factors / Q000276:immunology; D008168:Lung / Q000201:enzymology* / Q000276:immunology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D016328:NF-kappa B / Q000276:immunology*; D052247:Nitric Oxide Synthase Type II / Q000172:deficiency* / Q000276:immunology*; D018808:Transcription Factor AP-1 / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha
D016207:Cytokines; D007155:Immunologic Factors; D016328:NF-kappa B; D018808:Transcription Factor AP-1; D014409:Tumor Necrosis Factor-alpha; D052247:Nitric Oxide Synthase Type II