Mast cell derangement in salivary glands in patients with Sjogren's syndrome

Mast cells (MCs) have been implicated in many immune-inflammatory disorders . Deranged mast cell distribution and function may contribute to the local pathomechanisms in the labial salivary glands (LSG) in Sjogren's syndrome ( SS). Evidence for MC presence, localization frequency, subtype, and degree of activation was sought by using reverse transcriptase-polymerase chain re action (RT-PCR), immunohistochemistry (IHC)/image analysis, transmission el ectron microscopy, Western blotting, spectrophotometric activity assay, and radioimmunoassay. The overall expression (densitometric units) of MC trypt ase mRNA (1483 +/- 228 vs 1044 +/- 308) did not differ between SS and contr ol LSGs. However, IHC disclosed an uneven distribution of MCs in SS with an absence in lymphocyte foci and increased numbers (cells/mm(2) 77 +/- 7 vs 38 +/- 4, P < 0.01) elsewhere. Absence of MCs in the lymphocyte foci was no t a fixation artefact and was not explained by the presence of "phantom" MC s in these areas. In both SS and controls, 80% of all MCs were chymase cont aining, but the typical lattices/gratings characteristic for connective tis sue MCs (CTMCs) were not found. Instead, MC granules had mostly a homogeneo us, finely granular substructure characteristic of "new" granules subjected to a continuous, low-grade release. 32 kDa MC tryptase was found in saliva and its activity/concentration was comparable to that found in controls. H owever, tryptase output was low in SS (1.30 +/- 0.30 mu g/min vs 3.49 +/- 0 .66 mu g/min, P < 0.001). Normal LSGs contain mostly CTMCs, in close contac t with various resident and immigrant cells, characterized by a low-grade r elease of MC mediators. In SS this normal pattern is disturbed so that MCs are absent in lymphocyte foci (but increased elsewhere in the glands). The net salivary output of MC mediators is low in SS. This derangement of MCs m ay contribute to the pathogenesis of SS via multiple mechanisms.