Modes of epithelial cell death and repair in Sjogren's syndrome (SS)

We evaluated possible modes of epithelial cell destruction and restoration in minor salivary gland biopsies from patients with SS. Minor salivary glan d biopsies from 10 primary Sjogren's syndrome (pSS) patients and eight cont rol individuals were evaluated by immunohistochemical staining for the expr ession of apoptosis-related molecules, substances released by activated cyt otoxic T cells, as well as proteins involved in epithelial cell repair. The results were analysed by computer screen analysis and they were expressed as average percentages. Apoptosis-promoting molecules, Fas antigen and Fas ligand were observed in ductal and acinar epithelial cells as well as in in filtrating mononuclear cells of minor salivary glands from SS patients in c omparison with control biopsies. Bar protein, which acts as a death-promote r message, was expressed in the ductal and acinar epithelial cells and in m ononuclear infiltrating cells of SS patients compared with control individu als, while Bcl-2, an inhibitor of apoptosis, was primarily found in the lym phocytic infiltrates. In situ DNA fragmentation assay (TUNEL) revealed that epithelial cells were apoptotic in patients with SS compared with control subjects. Immunohistochemical staining for perforin and granzyme B, release d from granules of activated cytotoxic lymphocytes, revealed their presence in lymphocytic infiltrates of patients with SS compared with control biops ies. pS2, a member of the trefoil protein family which functions as promote r of epithelial cell repair and cell proliferation, was expressed in epithe lial cells in biopsies from SS patients. These studies suggest that the fun ctional epithelium of minor salivary glands in patients with SS appears to be influenced by both intrinsic and extrinsic mechanisms of destruction, wh ile a defensive mechanism of epithelial restoration seems to be active.