Contrasting effects of alveolar macrophages and neutrophils on asbestos-induced pulmonary epithelial cell injury.
Pulmonary toxicity from asbestos may be due in part to oxidant-mediated mechanisms. The purpose of this study was to determine whether alveolar macrophages (AM) contribute to asbestos-induced alveolar epithelial cell injury by oxidant-dependent mechanisms similar to that previously described for polymorphonuclear leukocytes (PMN). We assessed 51Cr release from cultured rat alveolar epithelial cells (RAEC) and transformed human pulmonary epithelial-like cell lines (rat L2 and human WI-26: HPEC). Amosite asbestos caused dose-dependent injury to both RAEC and L2 cells after an 18-h incubation period. Rat PMN increased asbestos-induced injury to RAEC (11 vs. 20% 51Cr release). In contrast, rat AM diminished asbestos-induced injury to RAEC and L2 cells by 60-80%. Human monocytes cultured for 72 h also attenuated asbestos-induced HPEC damage. Asbestos stimulated more H2O2 release from PMN than from AM isolated from the same rats (5.3 +/- 0.6 vs. 0.3 +/- 0.1 nmol x 10(6) cells-1 x 2h-1). The protective effect of rat AM, as opposed to PMN, was not due to differences in asbestos-induced toxicity to each cell type, since > 90% of AM and PMN were nonviable after 18 h. Transmission electron microscopy demonstrated comparable uptake of asbestos by AM and PMN after a 2-h incubation period. However, after an 18-h exposure period, the PMN were completely lysed, whereas over 90% of the AM contained fibers, despite morphologic evidence of cytotoxicity. These results demonstrate that AM, unlike PMN, can reduce alveolar epithelial cell injury in this model.(ABSTRACT TRUNCATED AT 250 WORDS)
Kamp
D W
DW
Department of Medicine, Northwestern University Medical School, Chicago, Illinois 60611.
Dunn
M M
MM
Sbalchiero
J S
JS
Knap
A M
AM
Weitzman
S A
SA
D000818:Animals; D001194:Asbestos / Q000009:adverse effects* / Q000493:pharmacokinetics; D002461:Cell Line, Transformed; D002470:Cell Survival / Q000187:drug effects; D004848:Epithelium / Q000473:pathology; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism; D008168:Lung / Q000473:pathology*; D008171:Lung Diseases / Q000209:etiology* / Q000473:pathology*; D016676:Macrophages, Alveolar / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D009504:Neutrophils / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D011650:Pulmonary Alveoli / Q000187:drug effects / Q000473:pathology; D051381:Rats
D001194:Asbestos; D006861:Hydrogen Peroxide