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Hesse, A. K.; Dorger, M.; Kupatt, C.; Krombach, F. (2004): Proinflammatory role of inducible nitric oxide synthase in acute hyperoxic lung injury. In: Respiratory Research 5:11


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.