A. Mikulowska-mennis et al., Lymphocyte migration to is mediated by vascular inflamed lacrimal glands cell adhesion molecule-1/alpha(4)beta(1) integrin, peripheral node addressin/L-selectin, and lymphocyte function-associated antigen-1 adhesion pathways, AM J PATH, 159(2), 2001, pp. 671-681
Citations number
46
Categorie Soggetti
Research/Laboratory Medicine & Medical Tecnology","Medical Research Diagnosis & Treatment
Sjogren's syndrome is an autoimmune disease characterized by inflammation a
nd destruction of lacrimal and salivary glands. The development of the infl
ammation requires die migration of lymphocytes from the blood into these ti
ssues. This migration involves multistep cascades with binding of lacrimal
gland endothelial adhesion molecules to their ligands on circulating lympho
cytes. We used nonobese diabetic mice, which develop autoinimune-mediated l
acrimal gland inflammation, as an experimental model to define the adhesion
molecules that control lymphocyte migration into inflamed lacrimal glands.
We found that vascular endothelia in inflamed areas of lacrimal gland expr
essed vascular cell adhesion molecule (VCAM)-1 and the peripheral node addr
essin (PNAd), but not mucosal addressin cell adhesion molecule-1. Most lymp
hocytes in the inflamed glands expressed alpha (4) integrin, L-selectin, an
d lymphocyte function-associated antigen (LFA)-1. In vivo studies revealed
that antibodies against VCAM-1, alpha (4) integrin, PNAd, L-selectin, or LF
A-I almost completely blocked lymphocyte migration from blood into inflamed
lacrimal glands. There was no inhibition of migration by antibodies agains
t mucosal addressin cell adhesion molecule-1 or alpha (4)beta (7), integrin
. These results indicate that endothelial/lymphocyte adhesion cascades invo
lving VCAM-1/alpha (4)beta (1) integrin, PNAd/L-selectin, and LFA-1 control
the migration of lymphocytes into inflamed lacrimal gland. These adhesion
molecules offer potential therapeutic targets to block the development of l
acrimal gland inflammation and destruction.