Serum promotes asbestos-induced injury to human pulmonary epithelial cells.
Asbestos exposure causes chronic interstitial pulmonary fibrosis. Injury to human pulmonary epithelial cells (HPEC) is speculated to precede the fibrotic response. We investigated whether asbestos, either alone or in conjunction with serum, injured cultured HPEC as assessed in a standard chromium 51 release assay. Amosite asbestos in serum-free media induced modest HPEC injury (9.4% +/- 3.3% Cr release), which was significantly enhanced (2.7-fold) in the presence of serum (25.5% +/- 4% Cr release). HPEC cytotoxicity was both asbestos and serum dose-dependent. Additionally, we demonstrated that, compared with HPEC injury induced by asbestos plus serum, (1) heat-decomplemented serum or serum fractions of a wide range of molecular weights were equipotent to fresh serum, (2) catalase, superoxide dismutase, or dimethylthiourea was not protective, (3) 3-aminobenzamide, which prevents oxidant-induced adenosine triphosphate depletion by inhibiting poly-adenosine diphosphate-ribose polymerase, afforded significant protection (32% decrease in HPEC injury), and (4) deferoxamine-treated asbestos was significantly less toxic to HPEC compared with untreated asbestos, causing a 57% decrease in HPEC cytotoxicity. Electron microscopic studies revealed that, compared with buffer, serum increased the amount of amosite asbestos along the surface and inside HPEC. Thus, amosite asbestos is cytotoxic to cultured HPEC and serum promotes this injurious effect by augmenting the interaction of asbestos with HPEC. These data suggest that this effect may occur by increasing intracellular oxidant stress mediated in part by the iron in asbestos.
Kamp
D W
DW
Department of Medicine, Northwestern University Medical School, Chicago, IL 60611.
Dunne
M
M
Anderson
J A
JA
Weitzman
S A
SA
Dunn
M M
MM
D001194:Asbestos / Q000494:pharmacology*; D001790:Blood Physiological Phenomena; D002374:Catalase / Q000494:pharmacology; D002461:Cell Line, Transformed; D004848:Epithelium / Q000187:drug effects / Q000473:pathology; D006801:Humans; D007502:Iron Chelating Agents / Q000494:pharmacology; D008168:Lung / Q000187:drug effects* / Q000473:pathology / Q000648:ultrastructure; D008854:Microscopy, Electron; D013482:Superoxide Dismutase / Q000494:pharmacology; D013890:Thiourea / Q000031:analogs & derivatives / Q000494:pharmacology
D007502:Iron Chelating Agents; D001194:Asbestos; C038983:1,3-dimethylthiourea; D002374:Catalase; D013482:Superoxide Dismutase; D013890:Thiourea