[Fas-Fas ligand system in silicosis patients]

The exposure to silica and related substances such as silicate (e.g. chrysotile asbestos; 3MgO.2SiO2.H2O) or silicone (-R2Si-O-)n, used in plastic surgery, has been known to induce autoimmune diseases. The pathogenesis of autoimmunity induced by such environmental factors, however, needs to be clarified. On the other hand, details about the relationship between autoimmunity and defective functioning of the Fas-Fas ligand system have been analyzed. In this report, we intend to summarize our results which suggest a suppressed apoptosis through the Fas-Fas ligand system in silicosis patients, and to speculate on the effects of silica on inappropriate cell survival which could induce the development of autoimmune reactions. We observed elevated levels of serum sFas and an increased expression of sFas mRNA in silicosis patients. sFas instead of membranous Fas binds competitively to the Fas ligand, and consequently, reduces the apoptosis of Fas positive cells. In addition, we observed polyclonal activation of human T cells by silica and silicate in vitro. In such cases, many autoreactive clones could be activated simultaneously. From these results, silica and silicate could play an important role in inducing autoimmune reactions by (1) repeated polyclonal activation of human T cells and (2) the suppression of apoptosis inducing the release of sFas into the sera of the patients.