Role of junctional adhesion molecule-like protein in mediating monocyte transendothelial migration.

OBJECTIVE:Monocyte migration across the vascular endothelium of blood vessels is a key early event in atherosclerosis. The mechanisms underlying monocyte transendothelial migration (TEM), however, are still not completely understood. Here we studied the role of junctional adhesion molecule-like protein (JAML) in regulating monocyte TEM. METHODS AND RESULTS:Firstly, by Western blot and flow cytometry, we showed that JAML was strongly expressed in monocytes and monocyte surface expression of JAML was upregulated by monocyte chemotaxis protein-1 stimulation. Both monocyte adhesion to and migration across tumor necrosis factor-alpha (TNFalpha) preactivated human microvascular endothelial cell (HMEC-1) monolayers were dose-dependently reduced by anti-JAML antiserum or soluble extracellular JAML recombinant. Secondly, short-term exposure of human monocytes and THP-1 cells to advanced glycation end products increased cell surface JAML expression, which was correlated with enhanced cell adhesion and TEM. In contrast, knockdown of JAML in THP-1 monocytes decreased both adhesion and transmigration of THP-1 monocytes. Finally, direct binding assay of the soluble JAML to HMEC-1 monolayers suggested that endothelial coxsackie and adenovirus receptor (CAR) may serve as one of the ligands for JAML. CONCLUSIONS:Monocytic JAML plays a critical role in regulating monocyte TEM probably via binding to the endothelial CAR and other tight junction-associated adhesive molecules.

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