Expression of selectins (CD62 E,L,P) and cellular adhesion molecules in primary Sjögren's syndrome: questions to immunoregulation.
Adhesion molecules are important signal transmitters of the immune system and may mediate the homing of leukocytes to sites of inflammation. The aim of this work was to examine the presence of selecting and cellular adhesion molecules on epithelial and endothelial cells in labial salivary glands (LSG) in Sjögren's syndrome (SS). LSG biopsies were obtained from patients with primary SS (n = 31) and normal subjects (n = 21). Cryostat sections were examined with indirect immunoperoxidase. Epithelial cells in LSG from both patients and controls expressed LFA-3 (CD58) and Hermes I (CD44). A significantly increased number of acinar and ductal epithelial cells in LSG from patients expressed class I MHC (74%, as mean percentage of ductal epithelial cells) (P < 0.05), HLA-DR (58%) (P < 0.0001), and HLA-DQ (11%) (P < 0.001). To a lesser extent limited ICAM-1 (CD54) epithelial expression (6%) was noted only in a few biopsies from patients but none of the controls. Epithelial cells did not express any of the selectins CD62 E, L, and P and sometimes they expressed sialyl Le(x) (a ligand for selectins). Although the number of endothelial structures expressing ICAM-1 (CD54), HLA-DR, HLA-DQ, and class I MHC (per surface area) was increased in patients (P < 0.05), this may be due to the total increase of number of endothelial structures (P < 0.05) (Von Willebrand factor +ve) as part of the chronic inflammatory process. A smaller proportion of endothelial structures expressed E-selectin (CD62 E) (32%) and to a lesser extent VCAM-1 (CD106) (approximately 7%) as detectable only in some LSG from patients. P-selectin (CD62 P) was demonstrated on about one-third of endothelial structures in LSG from patients. Infiltrating mononuclear cells expressed CD11a (68%), CD18 (73%), CD11b (13%), CD11c (21%), CD58 (13%), CD4 (44%), CD8 (17%), CD62L (L-selectin) (18%), CD49d (38%), CD49e (15%), CD2 (56%), and CD44 (77%). The relatively reduced number of CD62 L +ve lymphocytes may be due to shedding of that molecule after activation. Sialyl Le(x) was not detectable on infiltrating lymphocytes. Although infiltrating mononuclear cells were activated, as evidenced by their expression of HLA-DR (72%) and ICAM-1 (55%), they did not express IL-2Ralpha (CD25, confirmed by two antibodies 2A3 and ACT1) or IL-2Rbeta (CD122), except rarely (< or = 1%). In some biopsies, CD106 and CD11c were localized on lymphocytes at the central areas of periductal lymphoid follicles with the appearance of dendritic cells. We conclude that adhesion molecules probably play a major role in the pathogenesis of SS. The pattern of expression of these molecules demonstrates a regulated altered activation in the glands associated with this disease. The glands may be subject to specific regulatory factors, in addition to proinflammatory cytokines.
Aziz
K E
KE
School of Pathology, University of New South Wales, Sydney, Australia.
McCluskey
P J
PJ
Wakefield
D
D
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015815:Cell Adhesion Molecules / Q000096:biosynthesis*; D002465:Cell Movement / Q000276:immunology; D019040:E-Selectin / Q000096:biosynthesis; D004730:Endothelium, Vascular / Q000378:metabolism; D004848:Epithelium / Q000378:metabolism; D005260:Female; D006801:Humans; D016130:Immunophenotyping; D019041:L-Selectin / Q000096:biosynthesis; D008024:Ligands; D008297:Male; D008875:Middle Aged; D019007:P-Selectin / Q000096:biosynthesis; D019087:Selectins / Q000096:biosynthesis*; D012859:Sjogren's Syndrome / Q000276:immunology* / Q000378:metabolism* / Q000473:pathology
D015815:Cell Adhesion Molecules; D019040:E-Selectin; D008024:Ligands; D019007:P-Selectin; D019087:Selectins; D019041:L-Selectin