Interstitial pulmonary fibrosis is a potentially lethal, chronic response to lung injury. Although the biochemical mechanisms involved in the pathogenesis of interstitial pulmonary fibrosis are poorly understood, reactive oxygen species, which are known to play a role in inflammatory reactions, are believed to be involved in the progression of this disease. It has been proposed that the antioxidant enzyme, extracellular superoxide dismutase (EC-SOD), can protect against the progression of pulmonary fibrosis. To test the hypothesis that EC-SOD plays a central role in this disease, transgenic mice that overexpress EC-SOD and knockout mice that do not express EC-SOD will be utilized in a model of bleomycin- induced pulmonary fibrosis. We will determine whether altered levels of EC-SOD in transgenic and knockout mice alters the response to bleomycin-induced lung injury. In addition, we will examine EC-SOD expression and1or biodistribution during the early stages of fibrotic injury, to determine if alterations in EC-SOD activity early in the development of the disease are critical to the pathogenesis of pulmonary fibrosis. Finally, we will examine the interactive effects of nitric oxide, superoxide and EC-SOD in our model to determine if nitric oxide is involved in the oxidative damage associated with pulmonary fibrosis.
| Fattman, Cheryl L; Chang, Ling-Yi; Termin, Toni A et al. (2003) Enhanced bleomycin-induced pulmonary damage in mice lacking extracellular superoxide dismutase. Free Radic Biol Med 35:763-71 |
| Oury, Tim D; Schaefer, Lisa M; Fattman, Cheryl L et al. (2002) Depletion of pulmonary EC-SOD after exposure to hyperoxia. Am J Physiol Lung Cell Mol Physiol 283:L777-84 |
| Fattman, C L; Chu, C T; Kulich, S M et al. (2001) Altered expression of extracellular superoxide dismutase in mouse lung after bleomycin treatment. Free Radic Biol Med 31:1198-207 |
