DISTRIBUTION OF MANGANESE SUPEROXIDE-DISMUTASE MESSENGER-RNA IN NORMAL AND HYPEROXIC RAT LUNG

Aerobic metabolism requires a continuous oxygen supply, which in turn can form partially reduced species (free radicals) that damage cellula r components. To prevent this, organisms have elaborate free radical-s cavenging defenses that include the superoxide dismutases. The lungs a re unique in their role as an oxygen-gathering system, making these de fenses critical to lung integrity. Manganese superoxide dismutase (Mn- SOD) levels increase in rats exposed to sublethal doses of hyperoxia a nd correlate with the development of tolerance to higher levels of hyp eroxia. Although pulmonary Mn-SOD protein and mRNA levels both change with hyperoxia, the timing and levels differ dramatically. Lung hetero geneity makes extrapolation of data from whole tissue homogenates or c ultures difficult. In this study, in situ hybridization of Mn-SOD in t he lungs of adult rats exposed to air or to 85% 02 for 3 days was perf ormed. In animals exposed to either air or 85% O2, Mn-SOD transcripts were present in arterioles, the septal tips of alveolar ducts, alveola r type II cells, and mesothelial cells. Hyperoxic lung had an intense, continuous labeling of the pleura that was distinctly greater than th e intermittent labeling of the pleura found in control animals. The hi gh level of expression of Mn-SOD mRNA in alveolar duct septal tips in both control and O2-exposed animals may be secondary to increased aero bic activity in these regions, which contain collagen and elastin and are important stress-bearing elements in the lung. Alveolar type II ce lls are metabolically active secretory cells and thus may experience i ncreased endogenously generated oxidative stress. Pleural effusions ar e common after hyperoxic exposures, suggesting damage to the mesotheli um. Mn-SOD in this region may thus serve an adaptive and protective ro le. The presence of Mn-SOD message in arterioles could be part of a va sogenic regulatory mechanism in light of new evidence linking superoxi de anion to vascular tone and permeability.