This Article Full Text Full Text (PDF) All Versions of this Article: 25/4/729    most recent 01.ATV.0000157154.14474.3bv1 Submit a response Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Ostermann, G. Articles by Weber, C. Search for Related Content PubMed PubMed Citation Articles by Ostermann, G. Articles by Weber, C. Related Collections Pathophysiology Endothelium/vascular type/nitric oxide Mechanism of atherosclerosis/growth factors Other Vascular biology

(Arteriosclerosis, Thrombosis, and Vascular Biology. 2005;25:729.)
© 2005 American Heart Association, Inc.

Vascular Biology

Involvement of JAM-A in Mononuclear Cell Recruitment on Inflamed or Atherosclerotic Endothelium

Inhibition by Soluble JAM-A

Georg Ostermann; Line Fraemohs; Thomas Baltus; Andreas Schober; Michael Lietz; Alma Zernecke; Elisa A. Liehn; Christian Weber

From the Departments of Cardiovascular Molecular Biology (G.O., L.F., T.B., A.S., M.L., A.Z., E.A.L., C.W.), Cardiology (A.S., A.Z., C.W.), and Anesthesiology (T.B.), University Hospital, Aachen, Germany.

Correspondence to Dr Christian Weber, Kardiovaskuläre Molekularbiologie, Universitätsklinikum Aachen, Rheinisch-Westfälische Technische Hochschule, Pauwelsstr. 30, 52074 Aachen, Germany. E-mail cweber{at}ukaachen.de

Objective— The junctional adhesion molecule (JAM)-A on endothelium contributes to the inflammatory recruitment of mononuclear cells involving engagement of its integrin receptor lymphocyte function-associated antigen (LFA)-1. It is unknown whether these functions can be inhibited by soluble forms of JAM-A, whether JAM-A is expressed on atherosclerotic endothelium, and whether it participates in atherogenic recruitment of mononuclear cells.

Methods and Results— Adhesion assays revealed that LFA-1–mediated binding of mononuclear cells to intercellular adhesion molecule (ICAM)-1 or cytokine-costimulated endothelium was dose-dependently inhibited by soluble JAM-A.Fc (sJAM-A.Fc). Similarly, sJAM-A.Fc reduced stromal cell-derived factor (SDF)-1–triggered transendothelial chemotaxis of activated T cells and their SDF-1–triggered arrest on cytokine-costimulated endothelium under flow conditions. Immunofluorescence analysis revealed an upregulation of JAM-A on early atherosclerotic endothelium of carotid arteries from apolipoprotein E-deficient (apoE^–/–) mice fed an atherogenic diet. In ex vivo perfusion assays, pretreatment of mononuclear cells with sJAM-A.Fc inhibited their very late antigen (VLA)-4–independent accumulation on atherosclerotic endothelium of these arteries.

Conclusions— Soluble forms of JAM-A can be effectively applied to inhibit distinct steps of mononuclear cell recruitment on inflamed or atherosclerotic endothelium. In conjunction with its expression on atherosclerotic endothelium, this suggests a functional contribution of JAM-A to atherogenesis.

We studied the effect of soluble JAM-A (sJAM-A.Fc) on atherogenic recruitment of mononuclear cells. Because sJAM-A.Fc can inhibit distinct steps of mononuclear cell recruitment, ie, adhesion and transendothelial chemotaxis, on inflamed and atherosclerotic endothelium, our data suggest a functional contribution of JAM-A to atherogenesis.

Key Words: cell adhesion molecules • endothelium • inflammation • atherosclerosis

This article has been cited by other articles:

				X. Li, M. Stankovic, B. P.-L. Lee, M. Aurrand-Lions, C. N. Hahn, Y. Lu, B. A. Imhof, M. A. Vadas, and J. R. Gamble JAM-C Induces Endothelial Cell Permeability Through Its Association and Regulation of {beta}3 Integrins Arterioscler Thromb Vasc Biol, August 1, 2009; 29(8): 1200 - 1206. [Abstract] [Full Text] [PDF]

				R. R. Koenen, J. Pruessmeyer, O. Soehnlein, L. Fraemohs, A. Zernecke, N. Schwarz, K. Reiss, A. Sarabi, L. Lindbom, T. M. Hackeng, et al. Regulated release and functional modulation of junctional adhesion molecule A by disintegrin metalloproteinases Blood, May 7, 2009; 113(19): 4799 - 4809. [Abstract] [Full Text] [PDF]

				N. Bardin, M. Blot-Chabaud, N. Despoix, A. Kebir, K. Harhouri, J.-P. Arsanto, L. Espinosa, P. Perrin, S. Robert, F. Vely, et al. CD146 and its Soluble Form Regulate Monocyte Transendothelial Migration Arterioscler Thromb Vasc Biol, May 1, 2009; 29(5): 746 - 753. [Abstract] [Full Text] [PDF]

				J. M. van Gils, J. J. Zwaginga, and P. L. Hordijk Molecular and functional interactions among monocytes, platelets, and endothelial cells and their relevance for cardiovascular diseases J. Leukoc. Biol., February 1, 2009; 85(2): 195 - 204. [Abstract] [Full Text] [PDF]

				M. R. Cera, M. Fabbri, C. Molendini, M. Corada, F. Orsenigo, M. Rehberg, C. A. Reichel, F. Krombach, R. Pardi, and E. Dejana JAM-A promotes neutrophil chemotaxis by controlling integrin internalization and recycling J. Cell Sci., January 15, 2009; 122(2): 268 - 277. [Abstract] [Full Text] [PDF]

				A. Schober Chemokines in Vascular Dysfunction and Remodeling Arterioscler Thromb Vasc Biol, November 1, 2008; 28(11): 1950 - 1959. [Abstract] [Full Text] [PDF]

				E. A. Severson, L. Jiang, A. I. Ivanov, K. J. Mandell, A. Nusrat, and C. A. Parkos Cis-Dimerization Mediates Function of Junctional Adhesion Molecule A Mol. Biol. Cell, May 1, 2008; 19(5): 1862 - 1872. [Abstract] [Full Text] [PDF]

				E. Galkina and K. Ley Vascular Adhesion Molecules in Atherosclerosis Arterioscler Thromb Vasc Biol, November 1, 2007; 27(11): 2292 - 2301. [Abstract] [Full Text] [PDF]

				R. C. Becker Emerging Paradigms, Platforms, and Unifying Themes in Biomarker Science J. Am. Coll. Cardiol., October 30, 2007; 50(18): 1777 - 1780. [Full Text] [PDF]

				P. F. Bradfield, S. Nourshargh, M. Aurrand-Lions, and B. A. Imhof JAM Family and Related Proteins in Leukocyte Migration (Vestweber Series) Arterioscler Thromb Vasc Biol, October 1, 2007; 27(10): 2104 - 2112. [Abstract] [Full Text] [PDF]

				H. Waki, B. Liu, M. Miyake, K. Katahira, D. Murphy, S. Kasparov, and J. F.R. Paton Junctional Adhesion Molecule-1 Is Upregulated in Spontaneously Hypertensive Rats: Evidence for a Prohypertensive Role Within the Brain Stem Hypertension, June 1, 2007; 49(6): 1321 - 1327. [Abstract] [Full Text] [PDF]

				G. Mandicourt, S. Iden, K. Ebnet, M. Aurrand-Lions, and B. A. Imhof JAM-C Regulates Tight Junctions and Integrin-mediated Cell Adhesion and Migration J. Biol. Chem., January 19, 2007; 282(3): 1830 - 1837. [Abstract] [Full Text] [PDF]

				M. Lucerna, A. Zernecke, R. de Nooijer, S. C. de Jager, I. Bot, C. van der Lans, I. Kholova, E. A. Liehn, T. J. C. van Berkel, S. Yla-Herttuala, et al. Vascular endothelial growth factor-A induces plaque expansion in ApoE knock-out mice by promoting de novo leukocyte recruitment Blood, January 1, 2007; 109(1): 122 - 129. [Abstract] [Full Text] [PDF]

				A. Zernecke, E. A. Liehn, L. Fraemohs, P. von Hundelshausen, R. R. Koenen, M. Corada, E. Dejana, and C. Weber Importance of Junctional Adhesion Molecule-A for Neointimal Lesion Formation and Infiltration in Atherosclerosis-Prone Mice Arterioscler Thromb Vasc Biol, February 1, 2006; 26(2): e10 - e13. [Abstract] [Full Text] [PDF]

				M. Corada, S. Chimenti, M. R. Cera, M. Vinci, M. Salio, F. Fiordaliso, N. De Angelis, A. Villa, M. Bossi, L. I. Staszewsky, et al. Junctional adhesion molecule-A-deficient polymorphonuclear cells show reduced diapedesis in peritonitis and heart ischemia-reperfusion injury PNAS, July 26, 2005; 102(30): 10634 - 10639. [Abstract] [Full Text] [PDF]

				S. F. Mause, P. von Hundelshausen, A. Zernecke, R. R. Koenen, and C. Weber Platelet Microparticles: A Transcellular Delivery System for RANTES Promoting Monocyte Recruitment on Endothelium Arterioscler Thromb Vasc Biol, July 1, 2005; 25(7): 1512 - 1518. [Abstract] [Full Text] [PDF]