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Blood, 15 April 2006, Vol. 107, No. 8, pp. 3342-3349. Prepublished online as a Blood First Edition Paper on December 22, 2005; DOI 10.1182/blood-2005-07-2840. This Article Full Text Full Text (PDF) All Versions of this Article: 2005-07-2840v1 107/8/3342    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 Laumonnier, Y. Articles by Simmet, T. Search for Related Content PubMed PubMed Citation Articles by Laumonnier, Y. Articles by Simmet, T. Related Collections Hemostasis, Thrombosis, and Vascular Biology Phagocytes Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  PHAGOCYTES Identification of the annexin A2 heterotetramer as a receptor for the plasmin-induced signaling in human peripheral monocytes Yves Laumonnier, Tatiana Syrovets, Ladislav Burysek, and Thomas Simmet From the Department of Pharmacology of Natural Products and Clinical Pharmacology, University of Ulm, Germany. We have previously demonstrated that plasmin acts as a potent proinflammatory activator of human peripheral monocytes. Here we identify the annexin A2 heterotetramer, composed of annexin A2 and S100A10, as a receptor for the plasmin-induced signaling in human monocytes. Monocytes express the annexin A2 heterotetramer on the cell surface as shown by flow cytometry, fluorescence microscopy, and coimmunoprecipitation of biotinylated cell surface proteins. Binding of plasmin to annexin A2 and S100A10 on monocytes was verified by biotin transfer from plasmin labeled with a trifunctional cross-linker. Antibodies directed against annexin A2 or S100A10 inhibited the chemotaxis elicited by plasmin, but not that induced by fMLP. Further, down-regulation of annexin A2 or S100A10 in monocytes by antisense oligodeoxynucleotides impaired the chemotactic response to plasmin, but not that to fMLP. Antisense oligodeoxynucleotides similarly decreased the TNF- release by plasmin-stimulated, but not by LPS-stimulated, monocytes. At the molecular level, stimulation with plasmin, but not with catalytically inactivated plasmin, induced cleavage of annexin A2 and dissociation of the heterotetramer complex. Substitution of lysine to alanine in position 27 abolished the cleavage of recombinant annexin A2 in vitro. Together, these data identify the annexin A2 heterotetramer as a signaling receptor activated by plasmin via proteolysis. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: V. A. Swystun, B. Renaux, F. Moreau, S. Wen, M. A. Peplowski, M. D. Hollenberg, and W. K. MacNaughton Serine proteases decrease intestinal epithelial ion permeability by activation of protein kinase C{zeta} Am J Physiol Gastrointest Liver Physiol, July 1, 2009; 297(1): G60 - G70. [Abstract] [Full Text] [PDF] M. Wygrecka, L. M. Marsh, R. E. Morty, I. Henneke, A. Guenther, J. Lohmeyer, P. Markart, and K. T. Preissner Enolase-1 promotes plasminogen-mediated recruitment of monocytes to the acutely inflamed lung Blood, May 28, 2009; 113(22): 5588 - 5598. [Abstract] [Full Text] [PDF] M. Popovic, Y. Laumonnier, L. Burysek, T. Syrovets, and T. Simmet Thrombin-induced expression of endothelial CX3CL1 potentiates monocyte CCL2 production and transendothelial migration J. Leukoc. Biol., July 1, 2008; 84(1): 215 - 223. [Abstract] [Full Text] [PDF] Y. Zhang, Z.-H. Zhou, T. H. Bugge, and L. M. Wahl Urokinase-Type Plasminogen Activator Stimulation of Monocyte Matrix Metalloproteinase-1 Production Is Mediated by Plasmin-Dependent Signaling through Annexin A2 and Inhibited by Inactive Plasmin J. Immunol., September 1, 2007; 179(5): 3297 - 3304. [Abstract] [Full Text] [PDF] Q. Li, Y. Laumonnier, T. Syrovets, and T. Simmet Plasmin Triggers Cytokine Induction in Human Monocyte-Derived Macrophages Arterioscler Thromb Vasc Biol, June 1, 2007; 27(6): 1383 - 1389. [Abstract] [Full Text] [PDF] M. C. Derry, M. R. Sutherland, C. M. Restall, D. M. Waisman, and E. L. G. Pryzdial Annexin 2-mediated enhancement of cytomegalovirus infection opposes inhibition by annexin 1 or annexin 5 J. Gen. Virol., January 1, 2007; 88(1): 19 - 27. [Abstract] [Full Text] [PDF] G. Lu, H. Maeda, S. V. Reddy, N. Kurihara, R. Leach, J. L. Anderson, and G. D. Roodman Cloning and Characterization of the Annexin II Receptor on Human Marrow Stromal Cells J. Biol. Chem., October 13, 2006; 281(41): 30542 - 30550. [Abstract] [Full Text] [PDF]

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