RT Journal Article
SR Electronic
T1 Bleomycin increases superoxide anion generation by pig peripheral alveolar macrophages.
JF Molecular Pharmacology
JO Mol Pharmacol
FD American Society for Pharmacology and Experimental Therapeutics
SP 48
OP 52
VO 30
IS 1
A1 N S Conley
A1 J W Yarbro
A1 H A Ferrari
A1 R B Zeidler
YR 1986
UL http://molpharm.aspetjournals.org/content/30/1/48.abstract
AB 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.