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Silicosis patients not only suffer from respiratory disorders but also from autoimmune diseases. To clarify the mechanisms involved in the occurrence of the dysregulation of autoimmunity found in silicosis patients, we have been focusing on investigation of the Fas and Fas-related molecules in the Fas-mediated apoptotic pathway, since Fas is one of the most important molecules regulating autoimmunity in mainly T cells. Our findings showed that silicosis patients exhibited elevated serum soluble Fas levels, increased relative expression of soluble Fas and DcR 3 genes in peripheral blood mononuclear cells, other highly detectable variant messages of Fas transcripts, relatively decreased expression of several physiological inhibitors (Sentrin, I-Fline, ICAD/DFF45, and survivin), and dominancy of lower membrane Fas expressers in lymphocytes when compared with healthy volunteers. These parameters also constitute immunological factors with serum immunogulobulin G and the titer of anti-nuclear autoantibodies. In addition, anti-caspase 8 autoantibody and anti-Fas autoantibody were also detected in the serum from silicosis patients, and a functional assay showed that anti-Fas antibody stimulated Fas-mediated apoptosis. Taken together, we hypothesize that there are two subpopulations of silicosis lymphocytes. One is a long-term survival fraction including a self-recognizing fraction showing lower membrane Fas and inhibition of Fas/Fas ligand bindings in the extracellular region. The other is a fraction exhibiting apoptosis caused by silica/silicates, recruiting from bone marrow, showing higher membrane Fas and sensitive to anti-Fas autoantibody. Further investigations should be performed to confirm the effects of silica/silicates on the human immune system.

Early diagnosis of lung fibrosis has been hampered by the lack of a simple, convenient and specific method. Recently Rohde et al. developed an assay method for Type III procollagen peptide. Type III procollagen peptide, an extension peptide released during the biosynthesis of collagen Type III, has been known as a good marker for hepatic fibrosis. Therefore, we applied this assay to the patients with idiopathic pulmonary fibrosis, lung fibrosis in collagen disease and silicosis. And also we measured the serum level of the peptide in the healthy workers being exposed to silica. Normal value of the peptide in adults was 8.3 +/- 2.6 (mean +/- SD; n = 32) ng/ml. The upper value over mean + 2SD, 13.4 ng/ml, was regarded as abnormal value. Six patients with idiopathic pulmonary fibrosis, and lung fibrosis in collagen disease showed a significant increased level of 19.0 +/- 9.6 ng/ml (P less than 0.02). Four of 6 patients had abnormal high values. On the other hand, the patients with silicosis had not so high levels of peptide (12.6 +/- 6.5 ng/ml; n = 24; P less than 0.01), but 25% of the patients showed abnormal values. There were 2 cases among 19 healthy workers being exposed to silica who revealed slight abnormal values, 15.6 and 16.7 ng/ml. These observations suggest that the assay has a prognostic value for lung fibrosis and also is useful for the early detection of active lung fibrosis in the workers, even though Type III procollagen biosynthesis is already low in the late stages of silicosis.