The role of junctional adhesion molecule-C (JAM-C) in oxidized LDL-mediated leukocyte recruitment
Research output: Contribution to journal › Research article › Contributed › peer-review
Contributors
Abstract
The junctional adhesion molecule-C (JAM-C) was recently shown to be a counter receptor for the leukocyte beta2-integrin Mac-1 (CD11b/CD18), thereby mediating interactions between vascular cells, particularly in inflammatory cell recruitment. Here, we investigated the role of JAM-C in oxidized low-density lipoprotein (LDL)-mediated leukocyte recruitment. As compared with normal arteries, immunostaining of atherosclerotic vessels revealed a high expression of JAM-C in association with neointimal smooth muscle cells and the endothelium. Moreover, JAM-C was strongly up-regulated in the spontaneous early lesions in ApoE -/- mice. In vitro, cultured human arterial smooth muscle cells (HASMC) were found to express JAM-C, and oxLDL, as well as enzymatically modified LDL (eLDL) significantly up-regulated JAM-C on both HASMC and endothelial cells in a time- and dose-dependent manner. Although under quiescent conditions, JAM-C predominantly localized to interendothelial cell-cell contacts in close proximity to zonula occludens-1 (ZO-1), oxLDL treatment induced a disorganization of JAM-C localization that was no more restricted to the interendothelial junctions. JAM-C thereby mediated both leukocyte adhesion and leukocyte transendothelial migration upon oxLDL treatment of endothelial cells, whereas JAM-C on quiescent endothelial cells only mediates leukocyte transmigration. Thus, upon oxLDL stimulation endothelial JAM-C functions as both an adhesion, as well as a transmigration receptor for leukocytes. Taken together, JAM-C is up-regulated by oxLDL and may thereby contribute to increased inflammatory cell recruitment during atherosclerosis. JAM-C may therefore provide a novel molecular target for antagonizing interactions between vascular cells in atherosclerosis.
Details
Original language | English |
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Pages (from-to) | 2078-2080 |
Number of pages | 3 |
Journal | FASEB journal : official publication of the Federation of American Societies for Experimental Biology |
Volume | 19 |
Issue number | 14 |
Publication status | Published - Dec 2005 |
Peer-reviewed | Yes |
Externally published | Yes |
External IDs
Scopus | 28744455806 |
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Keywords
Keywords
- Aged, Animals, Aorta/pathology, Atherosclerosis/metabolism, Blotting, Western, CD11b Antigen/biosynthesis, CD18 Antigens/biosynthesis, Cell Adhesion, Cell Adhesion Molecules/chemistry, Cell Movement, DNA, Complementary/metabolism, Dose-Response Relationship, Drug, Endothelial Cells/pathology, Endothelium, Vascular/cytology, Enzyme-Linked Immunosorbent Assay, Female, Humans, Immunoglobulin G/chemistry, Immunoglobulins/chemistry, Immunohistochemistry, Inflammation, Leukocytes/cytology, Lipoproteins, LDL/metabolism, Male, Membrane Proteins/chemistry, Mice, Mice, Transgenic, Microscopy, Fluorescence, Middle Aged, Models, Biological, Monocytes/cytology, Muscle, Smooth, Vascular/cytology, Myocytes, Smooth Muscle/cytology, Oxygen/chemistry, Recombinant Fusion Proteins/metabolism, Recombinant Proteins/chemistry, Time Factors, Umbilical Veins/cytology, Up-Regulation