Human Mn-superoxide dismutase in pulmonary epithelial cells of transgenic mice confers protection from oxygen injury

J. R. Wispe, B. B. Warner, J. C. Clark, C. R. Dey, J. Neuman, S. W. Glasser, J. D. Crapo, L. Y. Chang, J. A. Whitsett

Research output: Contribution to journalArticlepeer-review

294 Scopus citations

Abstract

To test directly whether mitochondrial Mn-superoxide dismutase (Mn-SOD) protects the lung epithelium from oxygen-induced injury, transgenic mice were produced in which the expression of human Mn-SOD mRNA was directed by transcriptional elements from the human pulmonary surfactant protein C gene. Human Mn-SOD mRNA was expressed in a lung-specific manner, and increased Mn-SOD protein was detected within mitochondria of alveolar Type II and nonciliated bronchiolar cells of the distal respiratory epithelium of the transgenic mice. The activity of Mn-SOD, but not catalase, CuZn-SOD, or glutathione peroxidase, was increased in lungs of transgenic mice. Transgenic mice were highly protected from lung injury during exposure to 95% oxygen, surviving significantly longer than nontransgenic littermates. Pulmonary pathology demonstrated decreased hemorrhage, hyaline membrane formation, and alveolar and interstitial edema in transgenic animals. The finding that increased Mn-SOD in distal respiratory epithelial cells confers protection from oxygen injury provides a basis for novel therapies to protect lung from injury during oxygen therapy of acute and chronic lung diseases.

Original languageEnglish
Pages (from-to)23937-23941
Number of pages5
JournalJournal of Biological Chemistry
Volume267
Issue number33
StatePublished - Nov 25 1992

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