Increased oxidant resistance of alveolar epithelial type II cells. Isolated from rats following repeated exposure to cadmium aerosols.

Alveolar epithelial type II cells (AEIIC) were isolated from male Lewis rats following repeated in vivo cadmium aerosol exposure and were subsequently evaluated for their oxidant resistance in vitro. AEIIC from Cd-adapted animals removed a greater proportion of hydrogen peroxide from the extracellular milieu and incurred less oxidant-induced cytotoxicity than AEIIC from air controls. This altered response to oxidants occurred coincident with changes in cellular resistance factors. A two-fold increase in glutathione peroxidase activity and a 1.5-fold increase in the activities of glutathione reductase and catalase were observed in Cd-adapted AEIIC compared to control cells. These cells also exhibited a dramatic induction of metallothionein (MT), a thiol-rich protein known to scavenge free radicals in vitro. MT concentration increased as a function of exposure number. MT was localized within the nucleus and cytoplasm of AEIIC by immunocytochemical techniques. MT positive cells showed a wide variation of MT content, particularly in the nucleus. The biochemical and physiological features of these AEIIC may explain, in part, why animals pretreated with Cd aerosols develop cross-tolerance to hyperoxia.