Mast cell derangement in salivary glands in patients with Sjögren'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 reaction (RT-PCR), immunohistochemistry (IHC)/image analysis, transmission electron microscopy, Western blotting, spectrophotometric activity assay, and radioimmunoassay. The overall expression (densitometric units) of MC tryptase mRNA (1483 +/- 228 vs 1044 +/- 308) did not differ between SS and control LSGs. However, IHC disclosed an uneven distribution of MCs in SS with an absence in lymphocyte foci and increased numbers (cells/mm2 77 +/- 7 vs 38 +/- 4, P < 0.01) elsewhere. Absence of MCs in the lymphocyte foci was not a fixation artefact and was not explained by the presence of "phantom" MCs in these areas. In both SS and controls, 80% of all MCs were chymase containing, but the typical lattices/gratings characteristic for connective tissue MCs (CTMCs) were not found. Instead, MC granules had mostly a homogeneous, 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. However, tryptase output was low in SS (1.30 +/- 0.30 microg/min vs 3.49 +/- 0.66 microg/min, P < 0.001). Normal LSGs contain mostly CTMCs, in close contact with various resident and immigrant cells, characterized by a low-grade release 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 may contribute to the pathogenesis of SS via multiple mechanisms.
Konttinen
Y T
YT
Department of Anatomy, University of Helsinki, Finland.
Hietanen
J
J
Virtanen
I
I
Ma
J
J
Sorsa
T
T
Xu
J W
JW
Williams
N P
NP
Manthorpe
R
R
Janin
A
A
D000328:Adult; D000368:Aged; D053818:Chymases; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008407:Mast Cells / Q000201:enzymology* / Q000473:pathology*; D008854:Microscopy, Electron; D008875:Middle Aged; D012333:RNA, Messenger / Q000378:metabolism; D012469:Salivary Glands / Q000201:enzymology / Q000473:pathology* / Q000648:ultrastructure; D012697:Serine Endopeptidases / Q000235:genetics / Q000378:metabolism; D012859:Sjogren's Syndrome / Q000201:enzymology / Q000473:pathology*; D053802:Tryptases
D012333:RNA, Messenger; D012697:Serine Endopeptidases; C083294:chymase 2; D053818:Chymases; D053802:Tryptases