Bleomycin increases superoxide anion generation by pig peripheral alveolar macrophages.

Pulmonary fibrosis is the major toxic effect of bleomycin chemotherapy; however, the molecular mechanisms of the pathological process are unknown. Since alveolar macrophages produce toxic oxygen metabolites and these can damage lung cells, the effect of bleomycin on superoxide anion production was investigated in subpopulations of pig alveolar macrophages. Cells were lavaged from the lung and separated into three subpopulations according to their density. Their capacity to generate superoxide anions increased the more distally they were located. Bleomycin (5.0 milliunits/ml) increased the rate of superoxide production by 75 +/- 24% in dense alveolar macrophages located in the lung periphery. Hydrocortisone (10.0 micrograms/ml) inhibited this superoxide production by 33 +/- 10%. Results from this study suggest that an excess production of superoxide anions by alveolar macrophages may be the underlying cause of bleomycin pulmonary toxicity.