FAS AND FAS LIGAND EXPRESSION IN THE SALIVARY-GLANDS OF PATIENTS WITHPRIMARY SJOGRENS-SYNDROME

Objective. To assess the role of Fas-mediated apoptosis in the salivar y glands of patients with primary Sjogren's syndrome (SS). Methods. Ex pression of Fas, Fas ligand (FasL), and bcl-2 in salivary gland biopsy material was detected in situ by immunohistochemical staining and rev erse transcriptase-polymerase chain reaction. DNA fragmentation in apo ptotic cells was assessed by the enzymatic incorporation of labeled nu cleotides (digoxigenin-dUTP). Results. The acinar epithelial cells in SS were Fas+ and FasL+, and these cells died by apoptosis, The majorit y of infiltrating lymphocytes in SS were Fas+ and bcl-2+, while few ly mphocytes expressed FasL, In situ detection of apoptosis showed minima l cell death of lymphocytes, particularly in dense periductal foci. Ly mphocytic cell death was significantly lower (P < 0.0001) in these foc i compared with that in the interstitium. Conclusion. Infiltrating lym phocytes in the focal lesions of the salivary glands of patients with SS are blocked in their ability to commit to apoptosis, even though th ey may express Fas, The presence of bcl-2 in these cells may explain t heir inability to undergo apoptosis, The acinar epithelial cells, in c ontrast, may undergo Fas-mediated apoptosis, These results suggest tha t the Fas death pathway may be an important mechanism leading to the g landular destruction found in SS.