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% O-2) 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% O-2
or >95% O-2 for 72 h. Results: Exposure to >95% O-2 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. Conclusion: Taken together, our results
provide evidence to suggest that iNOS plays a proinflammatory role
in acute hyperoxic lung injury.