EXPRESSION OF SELECTINS (CD62 E,L,P) AND CELLULAR ADHESION MOLECULES IN PRIMARY SJOGRENS-SYNDROME - QUESTIONS TO IMMUNOREGULATION

Adhesion molecules are important signal transmitters of the immune sys tem and may mediate the homing of leukocytes to sites of inflammation. The aim of this work was to examine the presence of selectins and cel lular adhesion molecules on epithelial and endothelial cells in labial salivary glands (LSG) in Sjogren'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 LF A-3 (CD58) and Hermes I (CD44). A significantly increased number of ac inar and ductal epithelial cells in LSG from patients expressed class I MHC (74%, as mean percentage of ductal epithelial cells) (P < 0.05), HLDA-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 onl y 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 somet imes they expressed sialyl Le(x) (a ligand for selectins). Although th e number of endothelial structures expressing ICAM-1 (CD54), HLA-DR, H LA-DQ, and class IMHC (per surface area) was increased in patients (P < 0.05), this may be due to the total increase of number of endothelia l structures (P < 0.05) (Von Willebrand factor +ve) as part of the chr onic inflammatory process. A smaller proportion of endothelial structu res expressed E-selectin (CD62 E) (32%) and to a lesser extent VCAM-1 (CD106) (similar to 7%) as detectable only in some LSG from patients. P-selectin (CD62 P) was demonstrated on about one-third of endothelial structures in LSG: hom patients. Infiltrating mononuclear cells expre ssed CD11a (68%), CD18 (73%), CD11b (13%), CD11c (21%), CD58 (13%), CD 4 (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 activatio n. Sialyl Le(x) was not detectable on infiltrating lymphocytes. Althou gh infiltrating mononuclear cells were activated, as evidenced by thei r expression of HLA-DR (72%) and ICARI-1 (55%), they did not express I L-2R alpha (CD25, confirmed by two antibodies 2A3 and ACT1) or IL-2R b eta (CD122), except rarely (less than or equal to 1%). In some biopsie s, CD106 and CD11c were localized on lymphocytes at the central areas of periductal lymphoid follicles with the appearance of dendritic cell s. We conclude that adhesion molecules probably play a major role in t he pathogenesis of SS. The pattern of expression of these molecules de monstrates a regulated altered activation in the glands associated wit h this disease. The glands may be subject to specific regulatory facto rs, in addition to proinflammatory cytokines. (C) 1996 Academic Press, Inc.