Detection of alternatively spliced variant messages of Fas gene and mutational screening of Fas and Fas ligand coding regions in peripheral blood mononuclear cells derived from silicosis patients

Silicosis is clinically characterized not only by respiratory disorders but by immunological abnormalities such as the appearance of autoantibodies an d complications of autoimmune diseases. Dysregulation of apoptosis, particu larly in the Fas/Fas ligand (FasL) pathway, has been considered to play a r ole in the pathogenesis of autoimmune diseases. It has been found that seru m soluble Fas (sFas) levels are elevated in silicosis patients (SIL) and th e sFas message is dominantly expressed in peripheral blood mononuclear cell s (PBMC) derived from these individuals. In the present study, one tried to detect alternatively spliced variant messages including typical sFas messa ge and found four that were highly and frequently expressed, and which poss ess a signal peptide domain, but not transmembrane and signal transducing d omains, in PBMC derived from SIL. Functional mutations were not detected in Fas and Fast genes in silicosis PBMC, Still, alternative spliced variants of the Fas gene including typical sFas message appear to play an important role in the immunological dysregulation in SIL. (C) 2000 Elsevier Science B .V. All rights reserved.