Proinflammatory role of inducible nitric oxide synthase in acute hyperoxic lung injury

• Main Authors: Kupatt Christian, Dörger Martina, Hesse Anne-Karin, Krombach Fritz
• Format: Article
• Language: English
• Published: BMC 2004-09-01
• Series: Respiratory Research
• Online Access: http://respiratory-research.com/content/5/1/11

<p>Abstract</p> <p>Background</p> <p>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 <it>in vitro </it>and <it>in vivo</it>. In the present study, we used a murine hyperoxic model to evaluate the effects of iNOS deficiency on the inflammatory response.</p> <p>Methods</p> <p>Wild-type and iNOS-deficient mice were exposed to normoxia, 60% O₂or >95% O₂for 72 h.</p> <p>Results</p> <p>Exposure to >95% O₂resulted 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.</p> <p>Conclusion</p> <p>Taken together, our results provide evidence to suggest that iNOS plays a proinflammatory role in acute hyperoxic lung injury.</p>