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, Tom Carter

Research output: Contribution to journalArticle

61 Citations (Scopus)

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.
LanguageEnglish
Pages5282-5290
Number of pages9
JournalBlood
Volume111
Issue number11
DOIs
Publication statusPublished - 5 Feb 2008

Fingerprint

Weibel-Palade Bodies
von Willebrand Factor
Molecules
Interleukin-8
Exocytosis
Membrane Proteins
Fusion reactions
P-Selectin
Endothelial cells
Dextrans
Chemokines
Cytokines
Proteins
Membranes
Imaging techniques
Chemical analysis
Hemostasis
Organelles
Endothelial Cells

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

Cite this

Babich, V., Meli, A., Knipe, L., Dempster, J. E., Skehel, P., Hannah, M. J., & Carter, T. (2008). Selective release of molecules from weibel-palade bodies during a lingering kiss. Blood, 111(11), 5282-5290. https://doi.org/10.1182/blood-2007-09-113746
Babich, Victor ; Meli, Athinoula ; Knipe, Laura ; Dempster, John E. ; Skehel, Paul ; Hannah, Matthew J. ; Carter, Tom. / Selective release of molecules from weibel-palade bodies during a lingering kiss. In: Blood. 2008 ; Vol. 111, No. 11. pp. 5282-5290.
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Babich, V, Meli, A, Knipe, L, Dempster, JE, Skehel, P, Hannah, MJ & Carter, T 2008, 'Selective release of molecules from weibel-palade bodies during a lingering kiss' Blood, vol. 111, no. 11, pp. 5282-5290. https://doi.org/10.1182/blood-2007-09-113746

Selective release of molecules from weibel-palade bodies during a lingering kiss. / Babich, Victor; Meli, Athinoula; Knipe, Laura; Dempster, John E.; Skehel, Paul; Hannah, Matthew J.; Carter, Tom.

In: Blood, Vol. 111, No. 11, 05.02.2008, p. 5282-5290.

Research output: Contribution to journalArticle

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T1 - Selective release of molecules from weibel-palade bodies during a lingering kiss

AU - Babich, Victor

AU - Meli, Athinoula

AU - Knipe, Laura

AU - Dempster, John E.

AU - Skehel, Paul

AU - Hannah, Matthew J.

AU - Carter, Tom

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Y1 - 2008/2/5

N2 - 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.

AB - 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.

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KW - p-selectin

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KW - deficient mice

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KW - secretion

KW - atherosclerosis

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T2 - Blood

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Babich V, Meli A, Knipe L, Dempster JE, Skehel P, Hannah MJ et al. Selective release of molecules from weibel-palade bodies during a lingering kiss. Blood. 2008 Feb 5;111(11):5282-5290. https://doi.org/10.1182/blood-2007-09-113746