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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.
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Submitted September 20, 2007
Accepted January 30, 2008
Selective release of molecules from Weibel Palade bodies during a lingering kiss
Victor Babich, Athinoula Meli, Laura Knipe, John E. Dempster, Paul Skehel, Matthew J Hannah, and Tom Carter*
Division of Molecular Neuroendocrinology, MRC National Institute for Medical Research, London, United Kingdom
Department of Physiology and Pharmacology, University of Strathclyde, Glasgow, United Kingdom
Division of Neuroscience, University of Edinburgh, Edinburgh, United Kingdom
* Corresponding author; email: tcarter{at}nimr.mrc.ac.uk.
Exocytosis of specialized endothelial cell secretory organelles, Weibel Palade bodies (WPBs), is thought to play an important role in regulating haemostasis and intravascular inflammation. The major WPB core proteins are Von Willebrand factor (VWF) and its propolypeptide (Proregion), constituting >95% of the content. Although the composition of the WPB can be fine-tuned to include cytokines and chemokines (e.g. IL-8 and Eotaxin-3), it is generally assumed that WPB exocytosis is inextricably associated with secretion of VWF. Here we show that WPB 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 ~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 in size from 3KDa to 2MDa, 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.
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