Effect of Hyperoxia, Hypoxia, and Maturation on Superoxide Dismutase Activity in Isolated Alveolar Macrophages

The influence of ambient O2 tensions and of cell maturation on superoxide dismutase activity were studied in tissue culture--maintained mouse alveolar macrophages. Cultivation under hyperoxic conditions (PO2 about 640 mmHg) for 24 hours was associated with a significant increase in superoxide dismutase activity as compared with normoxic conditions (PO2 approximately 150 mmHg). (Hyperoxia: superoxide dismutase = 7.9 +/- 4.0 (SD); normoxia: superoxide dismutase = 4.4 +/- 1.7 units X mg cell protein-1 P less than 0.05). Hypoxic exposure (PO2 approximately 15 mmHg) was associated with a significant decrease in superoxide dismutase compared to normoxic controls (hypoxia: 2.2 +/- 0.6; normoxic: 3.8 +/- 0.6 units X mg protein-1 P less than 0.01). This decrease was found only after 168 hours of in vitro hypoxia. The in vitro maturation of alveolar macrophages cultivated in air was associated with a progressive increase in superoxide dismutase activity per 10(6) cells, although superoxide dismutase activity per unit protein remained constant. Molecular O2 may modify cell superoxide dismutase activity by altering intrinsic enzyme regulation. The increase in superoxide dismutase activity with hyperoxia and the decrease with hypoxia are consistent with but not unequivocally establish an important role for superoxide dismutase in protecting against cellular O2 toxicity.