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Blood, 15 July 2005, Vol. 106, No. 2, pp. 725-733. Prepublished online as a Blood First Edition Paper on April 12, 2005; DOI 10.1182/blood-2004-11-4416. This Article Full Text (PDF) Supplemental Figure All Versions of this Article: 2004-11-4416v1 106/2/725    most recent Alert me when this article is cited Alert me if a correction is posted 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 Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Khandoga, A. Articles by Krombach, F. Search for Related Content PubMed PubMed Citation Articles by Khandoga, A. Articles by Krombach, F. Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted November 18, 2004 Accepted March 23, 2005 Junctional adhesion molecule -A deficiency increases hepatic ischemia-reperfusion injury despite reduction of neutrophil transendothelial migration Andrej Khandoga*, Julia S Kessler, Herbert Meissner, Marc Hanschen, Monica Corada, Toshiyuki Motoike, Georg Enders, Elisabetta Dejana, and Fritz Krombach Institute for Surgical Research, Ludwig-Maximilians-University of Munich, Munich, Germany Institute of Pathology, Ludwig-Maximilians-University of Munich, Munich, Germany Department of Vascular Biology, Italian Foundation for Cancer Research Institute of Molecular Oncology, Milan, Italy The University of Texas Southwestern Medical Center at Dallas, Dallas, TX, USA * Corresponding author; email: andrej.khandoga{at}med.uni-muenchen.de. The endothelial receptors that control leukocyte transmigration in the postischemic liver are not identified. We investigated the role of junctional adhesion molecule-A (JAM-A), a receptor expressed in endothelial tight junctions, leukocytes and platelets, for leukocyte transmigration during hepatic ischemia-reperfusion (I/R) in vivo. We show that JAM-A is up-regulated in hepatic venular endothelium during reperfusion. I/R-induced neutrophil transmigration was attenuated in both JAM-A-/- and endothelial JAM-A-/- mice as well as in mice treated with an anti-JAM-A antibody, whereas transmigration of T cells was JAM-A-independent. Postischemic leukocyte rolling remained unaffected in JAM-A-/- and endothelial JAM-A-/- mice, whereas intravascular leukocyte adherence was increased. The extent of interactions of JAM-A-/- platelets with the postischemic endothelium was comparable with that of JAM-A+/+ platelets. The I/R-induced increase in the activity of ALT/AST and sinusoidal perfusion failure were not reduced in JAM-A-/- mice, while the number of TUNEL-positive hepatocytes was significantly higher. Thus, we show for the first time that JAM-A is up-regulated in hepatic venules and serves as an endothelial receptor of neutrophil transmigration, but it does not mediate leukocyte rolling, adhesion as well as platelet-endothelial cell interactions. JAM-A deficiency does not reduce I/R-induced microvascular and hepatocellular necrotic injury, but increases hepatocyte apoptosis, despite attenuation of neutrophil infiltration. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: B. Vollmar and M. D. Menger The Hepatic Microcirculation: Mechanistic Contributions and Therapeutic Targets in Liver Injury and Repair Physiol Rev, October 1, 2009; 89(4): 1269 - 1339. [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] 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] 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] A. Tabuchi, M. Mertens, H. Kuppe, A. R. Pries, and W. M. 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