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Blood, 1 June 2008, Vol. 111, No. 11, pp. 5282-5290. Prepublished online as a Blood First Edition Paper on February 5, 2008; DOI 10.1182/blood-2007-09-113746. This Article Full Text Full Text (PDF) Supplemental Figures and Videos All Versions of this Article: blood-2007-09-113746v1 111/11/5282    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 Babich, V. Articles by Carter, T. Search for Related Content PubMed PubMed Citation Articles by Babich, V. Articles by Carter, T. Related Collections Hemostasis, Thrombosis, and Vascular Biology Plenary Papers Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  PLENARY PAPER Selective release of molecules from Weibel-Palade bodies during a lingering kiss Victor Babich1, Athinoula Meli1, Laura Knipe1, John E. Dempster2, Paul Skehel3, Matthew J. Hannah1, and Tom Carter1 1 Division of Molecular Neuroendocrinology, Medical Research Councils (MRC), National Institute for Medical Research, London; 2 Department of Physiology and Pharmacology, University of Strathclyde, Glasgow; and 3 Division of Neuroscience, University of Edinburgh, Edinburgh, United Kingdom Exocytosis of specialized endothelial cell secretory organelles, Weibel-Palade bodies (WPBs), is thought to play an important role in regulating hemostasis and intravascular inflammation. The major WPB core proteins are Von Willebrand factor (VWF) and its propolypeptide (Proregion), constituting more than 95% of the content. Although the composition of the WPBs can be fine-tuned to include cytokines and chemokines (eg, interleukin-8 [IL-8] and eotaxin-3), it is generally assumed that WPB exocytosis is inextricably associated with secretion of VWF. Here we show that WPBs can undergo a form of exocytosis during which VWF and Proregion are retained while smaller molecules, such as IL-8, are released. Imaging individual WPBs containing fluorescent cargo molecules revealed that during weak stimulation approximately 25% of fusion events result in a failure to release VWF or Proregion. The WPB membrane protein P-selectin was also retained; however, the membrane tetraspannin CD63 was released. Accumulation or exclusion of extracellular fluorescent dextran molecules ranging from 3 kDa to 2 mDa show that these events arise due to the formation of a fusion pore approximately 12 nm in diameter. The pore behaves as a molecular filter, allowing selective release of WPB core and membrane proteins. WPB exocytosis is not inextricably associated with secretion of VWF. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Article in Blood Online: Slipping out the Weibel-Palade body Jan Voorberg Blood 2008 111: 5264-5265. [Full Text] [PDF] This article has been cited by other articles: J. A. Berriman, S. Li, L. J. Hewlett, S. Wasilewski, F. N. Kiskin, T. Carter, M. J. Hannah, and P. B. Rosenthal Structural organization of Weibel-Palade bodies revealed by cryo-EM of vitrified endothelial cells PNAS, October 13, 2009; 106(41): 17407 - 17412. [Abstract] [Full Text] [PDF] Y. Xiong, Y. Huo, C. Chen, H. Zeng, X. Lu, C. Wei, C. Ruan, X. Zhang, Z. Hu, M. Shibuya, et al. Vascular Endothelial Growth Factor (VEGF) Receptor-2 Tyrosine 1175 Signaling Controls VEGF-induced von Willebrand Factor Release from Endothelial Cells via Phospholipase C-{gamma}1- and Protein Kinase A-dependent Pathways J. Biol. Chem., August 28, 2009; 284(35): 23217 - 23224. [Abstract] [Full Text] [PDF] V. Babich, L. Knipe, L. Hewlett, A. Meli, J. Dempster, M. J. Hannah, and T. Carter Differential Effect of Extracellular Acidosis on the Release and Dispersal of Soluble and Membrane Proteins Secreted from the Weibel-Palade Body J. Biol. Chem., May 1, 2009; 284(18): 12459 - 12468. [Abstract] [Full Text] [PDF] C. Jang, Y. J. Koh, N. K. Lim, H. J. Kang, D. H. Kim, S. K. Park, G. M. Lee, C. J. Jeon, and G. Y. Koh Angiopoietin-2 Exocytosis Is Stimulated by Sphingosine-1-Phosphate in Human Blood and Lymphatic Endothelial Cells Arterioscler Thromb Vasc Biol, March 1, 2009; 29(3): 401 - 407. [Abstract] [Full Text] [PDF]

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