NO2-induced acute and chronic lung injury cause imbalance of glutathione metabolism in type II pneumocytes.

BACKGROUND: During inspiration the lung is exposed to numerous oxidants and therefore has developed a system of antioxidant defense. This organ, besides the liver, is the major source of glutathione (GSH) metabolism, from which type II pneumocytes are metabolically the most active cells. MATERIAL/METHODS: To analyze oxidative stress, rats were exposed to air (control) or to 10 ppm nitrogen dioxide (NO2) for 3 and 20 days to induce acute and chronic lung injury. As measure of oxidative stress, GSH/GSSG ratios in blood, bronchoalveolar lavage (BAL) and type II pneumocytes were determined. Lipid peroxidation (LPO) was also measured in type II cells. To investigate the basis of these observations, GSH metabolism in type II pneumocytes was studied, analyzing mRNA expression of gamma-glutamyl-cysteine synthetase (gamma-GCS), glutathione synthetase (GS), gamma-glutamyltranspeptidase (gamma-GT), glutathione peroxidases (GPXs) and glutathione reductase (GR). Furthermore, enzyme activities of GPX and GR were determined. RESULTS: In acute and chronic lung injury the GSH/GSSG ratio was reduced in blood and BAL, but there was no change in type II pneumocytes. LPO in type II cells was only reduced in acute lung injury. In both kinds of lung injury mRNA expression of gamma-GCS, GS and GPX3 decreased, while expression of gamma-GT and GR increased. GPX4 mRNA expression decreased in acute lung injury and increased in the chronic state. Enzyme activity of GPX and GR was generally increased in lung injury. CONCLUSIONS: In NO2 induced acute and chronic lung injury, GSH metabolism is imbalanced.

Differences in mRNA expression, protein content, and enzyme activity of superoxide dismutases in type II pneumocytes of acute and chronic lung injury.

The lung is protected against oxidative stress by a variety of antioxidants and type II pneumocytes seem to play an important role in antioxidant defense. Previous studies have shown that inhalation of NO2 results in acute and chronic lung injury. How the expression and enzyme activity of antioxidant enzymes are influenced in type II cells of different inflammatory stages has yet not been studied. To elucidate this question, we exposed rats to 10 ppm NO2 for 3 or 20 days to induce acute or chronic lung injury. From these and air-breathing rats, type II pneumocytes were isolated. The mRNA expression and protein content of CuZnSOD and MnSOD as well as total SOD-specific enzyme activity were determined. For the acute lung injury (3 d NO2), the expression of CuZnSOD mRNA was significantly increased, while MnSOD expression was significantly reduced after 3 days of NO2 exposure. For the chronic lung injury (20 d NO2), CuZnSOD expression was still enhanced, while MnSOD expression was comparable to control. In parallel to CuZnSOD mRNA expression, the protein amount was significantly increased in acute and chronic lung injury however MnSOD protein content exhibited no intergroup differences. Total SOD enzyme activity showed a significant decrease after 3 days of NO2 exposure and was similar to control after 20 days. We conclude that during acute and chronic lung injury in type II pneumocytes expression and protein synthesis of CuZnSOD and MnSOD are regulated differently.