on October 23, 2008
Published online before print October 23, 2008, doi: 10.1161/ATVBAHA.108.177717
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Submitted on May 1, 2008
Accepted on October 12, 2008
Role of Junctional Adhesion Molecule-Like Protein in Mediating Monocyte Transendothelial Migration
Ya-Lan Guo ;
From the Jiangsu Diabetes Research Center (Y.-L.G., R.B., D.-Q.L., C.-Y.Z., K.Z.), State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Jiangsu, China; the Department of Biology (C.X.-J.C., Y.L.), Georgia State University, Atlanta; and Jiangsu CDC-Nanjing University Joint Institute of Virology (K.Z.), Nanjing, Jiangsu, China.
* To whom correspondence should be addressed. E-mail: kzen{at}nju.edu.cn.
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-
(TNF) 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.
Key words: monocytes • JAML • AGEs • transmigration • endothelial