Quantitation and localization of pulmonary manganese superoxide dismutase and tumor necrosis factor alpha following exposure to ozone and nitrogen dioxide

Tumor necrosis factor alpha (TNF alpha) and manganese superoxide dismutase (MnSOD) are thought to play critical roles in the process of lung injury, r epair, and disease, The induction of TNF alpha and MnSOD were examined in a model of progressive pulmonary fibrosis along the length of the alveolar d uct in rats exposed for 1, 5, and 8 weeks to a combination of 0.8 ppm ozone and 14.4 ppm nitrogen dioxide. This oxidant injury model results in a trip hasic response with an initial inflammatory stage during weeks 1-3, followe d by a partial resolution at weeks 4-5, and a final stage of rapidly progre ssive fibrosis during weeks 6-8, Changes in TNF alpha and MnSOD labeling fo r the proximal and distal alveolar ducts of the lungs were quantified using immunohistochemistry and morphometric techniques at 1, 5, and 8 weeks of e xposure. A significant elevation in MnSOD was noted in alveolar macrophages and interstitial cells of the proximal and distal portions of the alveolar duct following 8 weeks of exposure. Labeling for TNF alpha only in the pro ximal region of the alveolar duct, was significantly increased in alveolar macrophages after 1 and 8 weeks of exposure, while a significant increase i n TNF alpha labeling of interstitial cells in proximal regions was noted at all time points. We conclude that MnSOD is elevated in areas of focal inju ry as well as the more distal protected areas of the lungs, while TNF alpha correlates strongly with both the temporal and spatial aspects of greatest cellular injury in the lungs.