INCREASED OXIDANT RESISTANCE OF ALVEOLAR MACROPHAGES ISOLATED FROM RATS REPEATEDLY EXPOSED TO CADMIUM AEROSOLS

This study investigated potential mechanisms of oxidant resistance in alveolar macrophages (AM) isolated from Lewis rats exposed repeatedly to cadmium aerosols. Macrophages from Cd-adapted animals exhibited sig nificantly greater resistance to oxidant-induced cytotoxicity than con trol cells when challenged with hydrogen peroxide in vitro. Elevations in glutathione peroxidase and glutathione reductase activities were a ssociated with increased oxidant tolerance but catalase activity was u nchanged. Metallothionein (MT) expression (protein and mRNA) was drama tically up-regulated in response to in vivo Cd exposure. A study using immunocytochemistry and in situ hybridization techniques revealed sig nificant heterogeneity in the expression of metallothionein by AMs. Th e percentage of AMs positive for MT (protein and mRNA) and the degree of MT expression within individual cells increased in response to addi tional Cd exposures. A putative state of activation was suggested by t he differences in size and number of inclusion bodies in macrophages f rom Cd-adapted animals and by secretion of a cytokine with interleukin -1-like characteristics. In summary, AMs from Cd-adapted animals are d istinguished from control cells with respect to: (1) increased oxidant resistance, (2) secretion of cytokines, (3) elevations in enzymes ass ociated with glutathione metabolism, and (4) up-regulation in metallot hionein expression.