Changes in distribution, morphology, and tumor necrosis factor-alpha secretion of alveolar macrophage subpopulations during the development of bleomycin-induced pulmonary fibrosis.

Previous studies indicate that heterogeneous alveolar macrophages (AM) play a pivotal role in events associated with bleomycin-induced pulmonary fibrosis. A critical role has been suggested for tumor necrosis factor-alpha (TNF-alpha), a product of activated macrophages, in this fibrotic process. The present study examined whether the characteristics and function (TNF-alpha secretion) of rat AM subpopulations were altered during the development of bleomycin-induced fibrosis. After intratracheal bleomycin treatment, AM were separated into 18 density-defined subpopulations. Bleomycin treatment altered the distribution and morphology of AM subpopulations of densities 1.017 to 1.061 g/ml at all time points studied (4, 14, and 28 days). Subpopulations of densities 1.090 to 1.141 g/ml were affected only at 4 days after bleomycin treatment. Tumor necrosis factor-alpha secretion increased with time in 14- and 28-day samples of bleomycin-treated rats, particularly in subpopulations of densities 1.075 to 1.097 g/ml. These data indicate that alterations in the distribution, morphology, and function of AM subpopulations accompany the development of bleomycin-induced pulmonary fibrosis. When coupled with previous studies suggesting that TNF-alpha plays a role in the fibrotic process in this disease model, these data indicate that AM of densities 1.075 to 1.097 g/ml are responsible for the production of TNF-alpha associated with bleomycin-induced pulmonary fibrosis.