PERTUSSIS TOXIN TREATMENT ALTERS MANGANESE SUPEROXIDE-DISMUTASE ACTIVITY IN LUNG - EVIDENCE FOR LUNG OXYGEN-TOXICITY IN AIR-BREATHING RATS

Exposure of rats to hyperoxia or to treatment with endotoxin, increase s lung manganese superoxide dismutase (MnSOD) gene expression. However , the paths by which these environmental signals are transduced into e nhanced MnSOD gene expression are unknown. We now provide evidence tha t heterotrimeric G proteins are invoiced in the hyperosia-induced incr ease in lung MnSOD gene expression but that pertussis toxin-sensitive G proteins are not involved in the endotoxin-induced elevation of lung MnSOD gene expression. We also show that treating rats with pertussis toxin decreased lung MnSOD activity similar to 50%. This decline in M nSOD activity occurred without a change in the lung activity of copper -zinc SOD, catalase, or glutathione peroxidase. In air-breathing rats, the pertussis toxin-induced decrease in MnSOD activity was associated with the development of lung edema, pleural effusion with a high conc entration of protein, and biochemical evidence of lung oxygen toxicity . Compared to air-breathing rats, maintenance of pertussis toxin-treat ed rats under hypoxic or hyperoxic conditions respectively decreased o r increased intrathoracic fluid. Endotoxin treatment elevated lung MnS OD activity and protected pertussis toxin-treated rats from an increas e in intrathoracic fluid.