Lymphocyte migration to inflamed lacrimal glands is mediated by vascular cell adhesion molecule-1/α4β1 integrin, peripheral node addressin/L-selectin, and lymphocyte function-associated antigen-1 adhesion pathways

• Published in: The American journal of pathology Vol. 159; no. 2; pp. 671 - 681
• Main Authors: MIKULOWSKA-MENNIS, Anna, BAOHUI XU, BERBERIAN, John M, MICHIE, Sara A
• Format: Journal Article
• Language: English
• Published: Bethesda, MD American Society for Investigative Pathology 01.08.2001
• Subjects: Biological and medical sciences; Medical sciences; Miscellaneous; Ophthalmology; Regular; Immunohistochemistry; Immunopathology; Animal model; Vascular cell adhesion molecule 1; Rat; Stomatology; Migration; Rodentia; Cell adhesion molecule; Autoimmune disease; Inflammation; Sjögren syndrome; Pathology; Eye disease; Vertebrata; Experimental disease; Mammalia; Lacrimal gland; Integrin; Mouse; Animal; Systemic disease; Immunofluorescence; Lymphocyte
• ISSN: 0002-9440; 1525-2191
• DOI: 10.1016/s0002-9440(10)61738-5

Sjogren’s syndrome is an autoimmune disease characterized by inflammation and destruction of lacrimal and salivary glands. The development of the inflammation requires the migration of lymphocytes from the blood into these tissues. This migration involves multistep cascades with binding of lacrimal gland endothelial adhesion molecules to their ligands on circulating lymphocytes. We used nonobese diabetic mice, which develop autoimmune-mediated lacrimal 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 expressed vascular cell adhesion molecule (VCAM)-1 and the peripheral node addressin (PNAd), but not mucosal addressin cell adhesion molecule-1. Most lymphocytes in the inflamed glands expressed α 4 integrin, L-selectin, and lymphocyte function-associated antigen (LFA)-1. In vivo studies revealed that antibodies against VCAM-1, α 4 integrin, PNAd, L-selectin, or LFA-1 almost completely blocked lymphocyte migration from blood into inflamed lacrimal glands. There was no inhibition of migration by antibodies against mucosal addressin cell adhesion molecule-1 or α 4 β 7 integrin. These results indicate that endothelial/lymphocyte adhesion cascades involving VCAM-1/α 4 β 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 lacrimal gland inflammation and destruction.