Fas and Fas ligand expression in the salivary glands of patients with primary Sjögren's syndrome

Abstract

Objective. To assess the role of Fas‐mediated apoptosis in the salivary glands of patients with primary Sjögren's syndrome (SS). Methods. Expression of Fas, Fas ligand (FasL), and bcl‐2 in salivary gland biopsy material was detected in situ by immunohistochemical staining and reverse transcriptase‐polymerase chain reaction. DNA fragmentation in apoptotic cells was assessed by the enzymatic incorporation of labeled nucleotides (digoxigenin‐dUTP). Results. The acinar epithelial cells in SS were Fas+ and FasL+, and these cells died by apoptosis. The majority of infiltrating lymphocytes in SS were Fas+ and bcl‐2+, while few lymphocytes expressed FasL. In situ detection of apoptosis showed minimal cell death of lymphocytes, particularly in dense periductal foci. Lymphocytic cell death was significantly lower (P < 0.0001) in these foci compared with that in the interstitium. Conclusion. Infiltrating lymphocytes in the focal lesions of the salivary glands of patients with SS are blocked in their ability to commit to apoptosis, even though they may express Fas. The presence of bcl‐2 in these cells may explain their inability to undergo apoptosis. The acinar epithelial cells, in contrast, may undergo Fas‐mediated apoptosis. These results suggest that the Fas death pathway may be an important mechanism leading to the glandular destruction found in SS.

Fas and Fas-mediated effects on a human salivary cell line in vitro: a model for immune-mediated exocrine damage in Sjögren's syndrome

“…Fas and FasL have also been recognized in SS (Jonsson et al, 1994;Kong et al, 1997). In the present study, labial minor salivary glands from healthy individuals and SS patients were found to express Fas and FasL.…”

“…Fas may also be involved in the pathogenesis of a number of human autoimmune connective tissue disorders, including systemic lupus erythematosus (SLE, Mysler et al, 1994;Emlen et al, 1994), rheumatoid arthritis (Rose et al, 1994) Hashimoto's thyroiditis (Tanimoto et al, 1995;Giordano et al, 1997) and Sjo È gren's syndrome (SS, Ogawa et al, 1996;Kong et al, 1997). SS is an autoimmune disorder characterized by oral and ocular dryness, diminished salivary and lacrimal function, and loss of exocrine parenchymal tissues with replacement by an active mononuclear infiltrate (Fox and Kang, 1992).…”

“…The mechanisms leading to the tissue changes seen in SS are not fully understood. Recently, Fas receptor has been identified on salivary epithelial cells in human labial minor salivary glands of SS patients (Jonsson et al, 1994;Kong et al, 1997); leading to speculation that this cell surface receptor may be involved in the immunopathogenesis of this disorder.…”

Activation of PKC is sufficient to induce an apoptotic program in salivary gland acinar cells

“…Induction of apoptosis via the FAS/FAS ligand pathway has been suggested to lead to the salivary gland destruction seen in the autoimmune disorder known as Sjo È gren's syndrome. 1 In addition, apoptosis of normal salivary cells in patients treated with head and neck irradiation or chemotherapeutics can result in reduced salivary gland function, or xerostomia. 2,3 The critical genes in the apoptotic process have been defined genetically in C. elegans, and biochemically in other species.…”

Autocrine/paracrine cell death in Hashimoto's thyroiditis

“…Implications of the activation of this signalling system may not be limited to the pathogenesis of HT. Recently, acinar epithelial cells from salivary glands in patients with Sjögren's syndrome were shown to express both Fas and FasL mRNA, and the cells died of apoptosis (10). The same signalling system may be activated in other inflammatory conditions in the thyroid leading to hypothyroidism, or even contribute to cell death in autoimmune endocrinopathies such as Addison's disease and insulin-dependent diabetes mellitus.…”