SOLUBLE FAS MESSENGER-RNA IS DOMINANTLY EXPRESSED IN CASES WITH SILICOSIS

Although it is well known that cases with silicosis exhibit various im munological abnormalities, the mechanisms involved in the occurrence o f immuno-dysfunction or dysregulation induced by silica compounds have not yet been determined. Fas is a well-known cell surface molecule th at is involved in the apoptosis pathway that belongs to the tumour nec rosis factor-receptor family. Soluble Fas (sFas) is produced as an alt ernatively spliced product of the Fas gene and protects cells from apo ptosis due to antagonization of the binding between membrane form of t he Fas gene (mFas) and the Fas ligand. To determine the role of the Fa s/Fas ligand system in silica-induced immunological abnormalities, we investigated Fas and Fas-ligand message expression levels using the mu ltiplex reverse transcription-polymerase chain reaction (RT-PCR) metho d with peripheral blood mononuclear cells from silicosis cases with no clinical symptoms of autoimmune diseases. Although the relative expre ssion levels of the Fas or Fas-ligand genes were not remarkably altere d in these cases, we observed the sFas message was dominantly expresse d compared with mFas expression. These results suggest that self-recog nizing clones in cases with silicosis survive for decades, escaping th e exclusion mechanisms induced by apoptosis. Then they cause the appea rance of autoantibodies and the acquisition of autoimmune diseases seq uentially.