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Blood, 15 September 2007, Vol. 110, No. 6, pp. 1864-1870. Prepublished online as a Blood First Edition Paper on June 4, 2007; DOI 10.1182/blood-2007-01-069674. This Article Full Text Full Text (PDF) All Versions of this Article: blood-2007-01-069674v1 110/6/1864    most recent Alert me when this article is cited 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 Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Jalkanen, S. Articles by Salmi, M. Search for Related Content PubMed PubMed Citation Articles by Jalkanen, S. Articles by Salmi, M. Related Collections Hemostasis, Thrombosis, and Vascular Biology Phagocytes Cell Adhesion and Motility Signal Transduction Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  HEMOSTASIS, THROMBOSIS, AND VASCULAR BIOLOGY The oxidase activity of vascular adhesion protein-1 (VAP-1) induces endothelial E- and P-selectins and leukocyte binding Sirpa Jalkanen1,2, Marika Karikoski1, Nathalie Mercier1, Kaisa Koskinen1, Tiina Henttinen1, Kati Elima1,2, Katriina Salmivirta1, and Marko Salmi1,2 1 MediCity Research Laboratory, University of Turku, and 2 National Public Health Institute, Turku, Finland Leukocyte migration from the blood into tissues is pivotal in immune homeostasis and in inflammation. During the multistep extravasation cascade, endothelial selectins (P- and E-selectin) and vascular adhesion protein-1 (VAP-1), a cell-surface–expressed oxidase, are important in tethering and rolling. Here, we studied the signaling functions of the catalytic activity of VAP-1. Using human endothelial cells transfected with wild-type VAP-1 and an enzymatically inactive VAP-1 point mutant, we show that transcription and translation of E- and P-selectins are induced through the enzymatic activity of VAP-1. Moreover, use of VAP-1–deficient animals and VAP-1–deficient animals carrying the human VAP-1 as a transgene show a VAP-enzyme activity–dependent induction of P-selectin in vivo. Up-regulation of P-selectin was found both in high endothelial venules in lymphoid tissues and in flat-walled vessels in noninflamed tissues. VAP-1 activity in vivo led to increased P-selectin–dependent binding of lymphocytes to endothelial cells. These data show that the oxidase reaction catalyzed by VAP-1 alters the expression of other molecules involved in the leukocyte extravasation cascade. Our findings indicate cross-talk between adhesion molecules involved in the tethering and rolling of leukocytes and show that VAP-1–dependent signaling can prime the vessels for an enhanced inflammatory response. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Article in Blood Online: Lock 'n' roll with VAP-1 Suchitra Sumitran-Holgersson Blood 2007 110: 1706-1707. [Full Text] [PDF] This article has been cited by other articles: Y. Zhang, T. Ohkuri, D. Wakita, Y. Narita, K. Chamoto, H. Kitamura, and T. Nishimura Sialyl lewisx antigen-expressing human CD4+ T and CD8+ T cells as initial immune responders in memory phenotype subsets J. Leukoc. Biol., September 1, 2008; 84(3): 730 - 735. [Abstract] [Full Text] [PDF] B. Petri, M. Phillipson, and P. Kubes The Physiology of Leukocyte Recruitment: An In Vivo Perspective J. Immunol., May 15, 2008; 180(10): 6439 - 6446. [Abstract] [Full Text] [PDF] K. Noda, S. Miyahara, T. Nakazawa, L. Almulki, S. Nakao, T. Hisatomi, H. She, K. L. Thomas, R. C. Garland, J. W. Miller, et al. Inhibition of vascular adhesion protein-1 suppresses endotoxin-induced uveitis FASEB J, April 1, 2008; 22(4): 1094 - 1103. [Abstract] [Full Text] [PDF] A. M. O'Rourke, E. Y. Wang, A. Miller, E. M. Podar, K. Scheyhing, L. Huang, C. Kessler, H. Gao, H.-T. Ton-Nu, M. T. MacDonald, et al. Anti-Inflammatory Effects of LJP 1586 [Z-3-Fluoro-2-(4-methoxybenzyl)allylamine Hydrochloride], an Amine-Based Inhibitor of Semicarbazide-Sensitive Amine Oxidase Activity J. Pharmacol. Exp. Ther., February 1, 2008; 324(2): 867 - 875. [Abstract] [Full Text] [PDF] A. Holt, D. J. Smith, L. Cendron, G. Zanotti, A. Rigo, and M. L. Di Paolo Multiple Binding Sites for Substrates and Modulators of Semicarbazide-Sensitive Amine Oxidases: Kinetic Consequences Mol. Pharmacol., February 1, 2008; 73(2): 525 - 538. [Abstract] [Full Text] [PDF] S. Jalkanen and M. Salmi VAP-1 and CD73, Endothelial Cell Surface Enzymes in Leukocyte Extravasation Arterioscler Thromb Vasc Biol, January 1, 2008; 28(1): 18 - 26. [Abstract] [Full Text] [PDF] K. Koskinen, S. Nevalainen, M. Karikoski, A. Hanninen, S. Jalkanen, and M. Salmi VAP-1-Deficient Mice Display Defects in Mucosal Immunity and Antimicrobial Responses: Implications for Antiadhesive Applications J. Immunol., November 1, 2007; 179(9): 6160 - 6168. [Abstract] [Full Text] [PDF]

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