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Blood, 1 June 2004, Vol. 103, No. 11, pp. 4150-4156. Prepublished online as a Blood First Edition Paper on February 19, 2004; DOI 10.1182/blood-2003-10-3685. This Article Full Text Full Text (PDF) All Versions of this Article: 2003-10-3685v1 103/11/4150    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 Fiedler, U. Articles by Augustin, H. G. Search for Related Content PubMed PubMed Citation Articles by Fiedler, U. Articles by Augustin, H. G. Related Collections Hemostasis, Thrombosis, and Vascular Biology Cell Adhesion and Motility Signal Transduction Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  HEMOSTASIS, THROMBOSIS, AND VASCULAR BIOLOGY The Tie-2 ligand Angiopoietin-2 is stored in and rapidly released upon stimulation from endothelial cell Weibel-Palade bodies Ulrike Fiedler, Marion Scharpfenecker, Stefanie Koidl, Anja Hegen, Verena Grunow, Jarno M. Schmidt, Wilhelm Kriz, Gavin Thurston, and Hellmut G. Augustin From the Department of Vascular Biology and Angiogenesis Research, Tumor Biology Center, Freiburg, Germany; Institute for Anatomy and Cell Biology, University of Heidelberg, Heidelberg, Germany; and Regeneron Pharmaceuticals, Tarrytown, NY. The angiopoietins Ang-1 and Ang-2 have been identified as ligands with opposing functions of the receptor tyrosine kinase Tie-2 regulating endothelial cell survival and vascular maturation. Ang-1 acts in a paracrine agonistic manner, whereas Ang-2 appears to act primarily as an autocrine antagonistic regulator. To shed further light on the complexity of autocrine/paracrine agonistic/antagonistic functions of the angiopoietin/Tie-2 system, we have studied Ang-2 synthesis and secretion in different populations of wild-type and retrovirally Ang-2–transduced endothelial cells. Endogenous and overexpressed endothelial cell Ang-2 is expressed in a characteristic granular pattern indicative of a cytoplasmic storage granule. Light and electron microscopic double staining revealed Ang-2 colocalization with von Willebrand factor, identifying Ang-2 as a Weibel-Palade body molecule. Costaining with P-selectin showed that storage of Ang-2 and P-selectin in Weibel-Palade bodies is mutually exclusive. Stored Ang-2 has a long half-life of more than 18 hours and can be secreted within minutes of stimulation (eg, by phorbol 12-myristate 13-acetate [PMA], thrombin, and histamine). Collectively, the identification of Ang-2 as a stored, rapidly available molecule in endothelial cells strongly suggests functions of the angiopoietin/Tie-2 system beyond the established roles during angiogenesis likely to be involved in rapid vascular homeostatic reactions such as inflammation and coagulation. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: P Kumpers, S David, M Haubitz, J Hellpap, R Horn, V Brocker, M Schiffer, H Haller, and T Witte The Tie2 receptor antagonist angiopoietin 2 facilitates vascular inflammation in systemic lupus erythematosus Ann Rheum Dis, October 1, 2009; 68(10): 1638 - 1643. [Abstract] [Full Text] [PDF] Y. C. Yung, J. Chae, M. J. Buehler, C. P. Hunter, and D. J. Mooney Cyclic tensile strain triggers a sequence of autocrine and paracrine signaling to regulate angiogenic sprouting in human vascular cells PNAS, September 8, 2009; 106(36): 15279 - 15284. 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