Long-Lasting Production of TGF-β1 by Alveolar Macrophages Exposed to Low Doses of Asbestos without Apoptosis

Alveolar macrophages (AMs) exposed to asbestos are well known to produce TNF-α, which induces the production of TGF-β1, leading to lung fibrogenesis. The present study examines the production of TGF-β1 by AMs exposed to chrysotile B asbestos (CH) in vivoor in vitroand the relationship between TGF-β1 production and apoptosis in cultures of AMs. Rats instilled with CH via the trachea showed increases in TNF-α, IL-1β and IL-6 in the bronchoalveolar lavage fluid (B ALF) 1 day after the instillation, followed by increases in TGF-β1 and apoptotic cells 5 days after. The AMs from these BALFs produced a significantly increased amount of TGF-β1 in culture compared to those from the control rats. The addition of 2.5 μg/cm2of CH augmented the production of TGF-β1 by the AMs from the control to the same level as produced by the AMs from the CH-treated rats. The apoptosis of AMs was not induced at 2.5 μg/cm2of CH, but was drastically induced at over 12.5 μg/cm2. In contrast, the production of TGF-β1 by AMs peaked at around 2.5 μg/cm2of CH, and it lasted for 11 days. In addition, Bcl-2 and Bcl-xLincreased in the AMs surviving under the exposure to CH. Taken together, these results indicate that AMs can autonomously, without other pulmonary cells, acquire the lasting ability to produce TGF-β1 independently of apoptosis under low exposure to CH. The AMs with the lasting production of TGF-β1 may contribute not only to lung fibrosis but also to immune suppression.