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 · 10⁶ cells^-1 · 2 h^-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. The contrasting effects observed between AM and PMN can be explained in part by differences in asbestos-induced phagocyte H₂O₂ release and asbestos uptake. In conclusion, AM and PMN have distinct effects in modulating asbestos-induced alveolar epithelial cell injury. These effects may account for the relationship between increased numbers of PMN, but not AM, and abnormal gas exchange in asbestos workers.