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Am. J. Respir. Cell Mol. Biol., Volume 18, Number 4, April, 1998 538-547

Transgenic Models for the Study of Lung Antioxidant Defense: Enhanced Manganese-containing Superoxide Dismutase Activity Gives Partial Protection to B6C3 Hybrid Mice Exposed to Hyperoxia

Ye-Shih Ho, Renaud Vincent,* Margaret S. Dey, Jan W. Slot, and James D. Crapo

Institute of Chemical Toxicology, Wayne State University, Detroit, Michigan; Division of Pulmonary and Critical Care Medicine, Department of Medicine, Duke University Medical Center, Durham, North Carolina; and Department of Cell Biology, Medical School, State University of Utrecht, Utrecht, The Netherlands

To investigate the role of manganese-containing superoxide dismutase (MnSOD) in lung antioxidant defense, lines of transgenic B6C3 hybrid mice carrying human MnSOD transgenes under the transcriptional control of a human beta -actin promoter were established. Expression studies demonstrated that the human MnSOD transgene in line TgHMS66 is expressed and functional. The cellular distribution of the transgene product in the lungs was further examined by immunocytochemical analysis. Increased immunoreactive MnSOD was found in mitochondria of lung type I epithelial cells, type II epithelial cells, capillary endothelial cells, and fibroblasts. Furthermore, the magnitude of increase in mitochondrial labeling density of type II cells of nontransgenic, hemizygous, and homozygous transgenic littermates was proportional to the increased lung activity of MnSOD found in these mice. Transgenic mice over-expressing MnSOD did not have enhanced survival relative to controls when exposed to > 99% oxygen. However, when exposed to 90% oxygen, the transgenic mice had a small but statistically significant increase in survival time. Our results indicate that when the beta -actin promoter is used to increase activity of MnSOD it provides modest protection to B6C3 mice against hyperoxic lung injury.

*   Present address: Environmental and Toxicology Division, 0803C Environmental Health Center, Tunney's Pasture, Ottawa, ON K1A 0L2, Canada.




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Copyright © 1998 American Thoracic Society.