INCREASED EXPRESSION OF MANGANESE-CONTAINING SUPEROXIDE-DISMUTASE IN RAT LUNGS AFTER INHALATION OF INFLAMMATORY AND FIBROGENIC MINERALS

Steady-state mRNA levels and immunoreactive protein for manganese-cont aining superoxide dismutase (MnSOD) were assayed in rat lungs after su bchronic inhalation of the fibrogenic silicon dioxide, cristobalite, o r preparations of titanium dioxide (TiO2) of different inflammatory an d fibrogenic potential. Total and differential cell counts recoverable by bronchoalveolar lavage (BAL) were also measured to ascertain wheth er induction of certain antioxidant enzymes (AOE) correlated with infl ammatory responses. Inhalation of cristobalite and ultra-fine TiO2, a particle causing pulmonary inflammation and fibrosis, caused dramatic increases in MnSOD mRNA levels in rat lung which correlated with incre ases in MnSOD immunoreactive protein. Increases in gene expression of other AOE [catalase, glutathione peroxidase (GPX), copper-zinc contain ing superoxide dismutase (CuZnSOD)] were less striking and did not cor relate precisely with inflammatory changes in BAL correlated directly with steady-state MnSOD mRNA levels in lung. Inhalation of TiO2-F, a n oninflammatory, nonfibrogenic mineral, failed to induce MnSOD or mRNAs for other AOE. Our data suggest that particles causing inflammation a nd pulmonary fibrosis increase expression of AOE in lung, most notably MnSOD. Thus, elevations of MnSOD mRNA levels in lung or BAL may be pr edictive of lung disease.