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.