Inhibition of alveolar macrophage cytotoxicity by asbestos: possible role of prostaglandins.
Asbestosis and silicosis are chronic, fibrosing lung diseases due to prolonged inhalation of asbestos fibers or silica particles. However, little is known about the implication of these toxic dusts on cell-mediated cytotoxicity. Among the first types of cells that are in contact with the dusts are the alveolar macrophages (AM). We studied the effect of different concentrations of UICC chrysotile asbestos and silica on 18-h cytotoxicity of AM against tumor necrosis factor (TNF)-resistant P815 target cells or TNF-sensitive L929 target cells. Rat AM, obtained by bronchoalveolar lavage, were incubated for 2 h with 20, 50, or 100 micrograms/ml chrysotile or silica before the addition of target cells. AM cytotoxicity was significantly inhibited at greater than 20 micrograms/ml of chrysotile. In contrast, silica did not inhibit AM-mediated cytotoxicity at any concentration used. Asbestos, but not silica, caused significant production of PGE2 by macrophages and target cells. Addition of the cyclooxygenase inhibitor indomethacin to our system abolished all inhibition by asbestos. These results suggest that the inhibition of AM-mediated cytotoxicity by chrysotile was caused by prostaglandins, and that fibrogenic particles differ in their capacity to modulate AM function.
Bissonnette
E
E
Immunology Division, Faculty of Medicine, University of Sherbrooke, Québec, Canada.
Carré
B
B
Dubois
C
C
Rola-Pleszczynski
M
M
D000818:Animals; D001194:Asbestos / Q000494:pharmacology / Q000633:toxicity*; D002460:Cell Line; D003470:Culture Media / Q000494:pharmacology; D003602:Cytotoxicity, Immunologic / Q000187:drug effects; D004351:Drug Resistance; D008264:Macrophages / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D011453:Prostaglandins / Q000378:metabolism / Q000502:physiology; D011650:Pulmonary Alveoli / Q000166:cytology / Q000187:drug effects; D051381:Rats; D011919:Rats, Inbred Strains; D012822:Silicon Dioxide / Q000494:pharmacology / Q000633:toxicity; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D003470:Culture Media; D011453:Prostaglandins; D014409:Tumor Necrosis Factor-alpha; D001194:Asbestos; D012822:Silicon Dioxide