Involvement of Fas/Fas ligand in the induction of apoptosis in chronic sialadenitis of minor salivary glands including Sjögren's syndrome

Abstract

The role of apoptosis and contribution of Fas/FasL systems in the pathogenesis of Sjogren's syndrome (SS) are still controversial. With serial sections, we explored apoptosis assessed by the dUTP nick end labeling (TUNEL) method and expression of Fas and FasL by immunohistochemistry, and compared their distribution in minor salivary gland (MSG) of SS and sialolithiasis (SIL) patient tissues. Fas and FasL were co-localized in ductular and acinar cells of SS and SIL TUNEL+ cells co-distributed with the Fas and FasL expressing cells in ductular and acinar cells of SS in the vicinity of lymphocytic infiltration, while not in those of SIL Moreover, to morphologically confirm apoptosis, we identified TUNEL-positive(+) cells in the MSGs of SS at the ultra structural level by applying an inversion method to paraffin-embedded sections stained by TUNEL method. Surprisingly, these cells did not show characteristic apoptotic figures although TUNEL products were deposited on the hyperchromatin of acinar and ductular cells. On the other hand, acinar and ductular cells of SIL included clusters of TUNEL+ apoptotic bodies as did those cells by phagocytosis or having fallen into the ductular lumen. These findings suggest that Fas and FasL expressed in ducts and acini of chronic sialadenitis in SS patients induce apoptosis, possibily in an autocrine and/or paracrine manner.