Fas ligand and silicosis

Silicosis is a lung disease of the industrial age caused by the inhalation of silica. It is still a common and life-threatening occupational disease, particularly in the mining industry. Silicosis starts with inflammation and tissue destruction, followed by tissue repair leading to fibrosis. Pulmonary macrophages ingest the silica, and release a range of inflammatory mediators, most notably TNF. The resulting recruitment of neutrophils promotes the destruction of connective tissue. A recent study by Borges et al. now demonstrates a central role for Fas ligand (FasL) expressed on pulmonary macrophages in the induction of pulmonary silicosis. In a murine model of silicosis, they demonstrate that FasL-deficient mice do not develop the disease. These mice had markedly reduced neutrophil extravasation into bronchoalveolar spaces and decreased production of TNF. The transfer of wild-type macrophages expressing FasL into the mice induced silicosis, and a neutralizing anti-FasL Ab prevented silicosis in wild-type mice. FasL appears to play a role in inducing the apoptosis of macrophages following their ingestion of silica. This might lead to the release of IL-1, IL-18 and neutrophil chemoattractants from the dying macrophages. FasL itself has also been shown to be chemotactic for neutrophils. The study might have relevance for other inflammatory diseases of the lungs and might point the way to new therapies. J. Exp. Med. (2001) 194, 155–163. LON