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Selective release of molecules from weibel-palade bodies during a lingering kiss

Babich, Victor and Meli, Athinoula and Knipe, Laura and Dempster, John E. and Skehel, Paul and Hannah, Matthew J. and Carter, Tom (2008) Selective release of molecules from weibel-palade bodies during a lingering kiss. Blood, 111 (11). pp. 5282-5290. ISSN 0006-4971

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Abstract

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.

Item type: Article
ID code: 12943
Keywords: molecules, weibel-palade bodies, kiss, blood, biomedical sciences, von-willebrand-factor, human endothelial-cells, red fluorescent protein, p-selectin, fusion pore, deficient mice, exocytosis, secretion, atherosclerosis, Therapeutics. Pharmacology, Pharmacy and materia medica, Microbiology, Biochemistry, Cell Biology, Immunology, Hematology
Subjects: Medicine > Therapeutics. Pharmacology
Medicine > Pharmacy and materia medica
Science > Microbiology
Department: Faculty of Science > Strathclyde Institute of Pharmacy and Biomedical Sciences
Related URLs:
Depositing user: Ms Ann Barker-Myles
Date Deposited: 26 Aug 2009 14:54
Last modified: 04 Sep 2014 22:36
URI: http://strathprints.strath.ac.uk/id/eprint/12943

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