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-α concentration in the bronchoalveolar lavage fluid compared to iNOS knockout mice. Moreover, binding activity of NF-κB 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.