Bleomycin causes alveolar macrophages from cigarette smokers to release hydrogen peroxide.
Alveolar macrophages (AM) were retrieved by bronchoalveolar lavage from 20 patients. Following AM purification by glass adherence, the effect of bleomycin on hydrogen peroxide and lactic dehydrogenase release was assessed by colorimetric methods. All AM from nine nonsmokers had no detectable spontaneous release of hydrogen peroxide. The AM did not release hydrogen peroxide when stimulated with bleomycin (25 mU/mL). AM from all eleven smokers spontaneously released hydrogen peroxide (36 +/- 5.3 nm/10(6) AM, mean +/- SEM). AM from eight of the eleven smokers released more hydrogen peroxide when incubated with bleomycin (smokers 55 +/- 6.8 nm/10(6) AM, p less than 0.05). There was no difference in the amount of lactic dehydrogenase released by AM spontaneously or when incubated with bleomycin at 25 mU/mL, suggesting that this dose of bleomycin was not directly toxic to the AM. Results from this study further support the premise that bleomycin pulmonary toxicity may result from the generation of reactive oxygen metabolites and that cigarette smoking may predispose to bleomycin pulmonary toxicity.
D001761:Bleomycin / Q000009:adverse effects / Q000494:pharmacology*; D005260:Female; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism*; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008264:Macrophages / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D011650:Pulmonary Alveoli / Q000166:cytology*; D011658:Pulmonary Fibrosis / Q000139:chemically induced; D012907:Smoking / Q000378:metabolism*
D001761:Bleomycin; D006861:Hydrogen Peroxide; D007770:L-Lactate Dehydrogenase