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Superoxide Dismutases in the Lung and Human Lung Diseases

Departments of Medicine, University of Helsinki and University of Oulu, Finland; and National Jewish Medical and Research Center and University of Colorado Health Sciences Center, Denver, Colorado

Correspondence and requests for reprints should be addressed to James D. Crapo, M.D., National Jewish Medical and Research Center, Room K701, 1400 Jackson Street, Denver, CO 80206. E-mail: crapoj{at}njc.org

The lungs are directly exposed to higher oxygen concentrations than most other tissues. Increased oxidative stress is a significant part of the pathogenesis of obstructive lung diseases such as asthma and chronic obstructive pulmonary disease, parenchymal lung diseases (e.g., idiopathic pulmonary fibrosis and lung granulomatous diseases), and lung malignancies. Lung tissue is protected against these oxidants by a variety of antioxidant mechanisms among which the superoxide dismutases (SODs) are the only ones converting superoxide radicals to hydrogen peroxide. There are three SODs: cytosolic copper–zinc, mitochondrial manganese, and extracellular SODs. These enzymes have specific distributions and functions. Their importance in protecting lung tissue has been confirmed in transgenic and knockout animal studies. Relatively few studies have been conducted on these enzymes in the normal human lung or in human lung diseases. Most human studies suggest that there is induction of manganese SOD and, possibly, extracellular SOD during inflammatory, but not fibrotic, phases of parenchymal lung diseases and that both copper–zinc SOD and manganese SOD may be downregulated in asthmatic airways. Many previous antioxidant therapies have been disappointing, but newly characterized SOD mimetics are being shown to protect against oxidant-related lung disorders in animal models.

Key Words: free radicals • oxidants • antioxidants

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