Sphingosine-1-phosphate receptor 3 mediates sphingosine-1-phosphate induced release of Weibel-Palade bodies from endothelial cells

Kathinka W.E.M. Van Hooren, Léon J.A. Spijkers, Dorothee Van Breevoort, Mar Fernandez-Borja, Ruben Bierings, Jaap D. Van Buul, Astrid E. Alewijnse, Stephan L.M. Peters, Jan Voorberg*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

24 Citations (Scopus)
14 Downloads (Pure)


Sphingosine-1-phosphate (S1P) is an agonist for five distinct G-protein coupled receptors, that is released by platelets, mast cells, erythrocytes and endothelial cells. S1P promotes endothelial cell barrier function and induces release of endothelial cell-specific storage-organelles designated Weibel-Palade bodies (WPBs). S1P-mediated enhancement of endothelial cell barrier function is dependent on S1P receptor 1 (S1PR1) mediated signaling events that result in the activation of the small GTPase Rac1. Recently, we have reported that Rac1 regulates epinephrine-induced WPB exocytosis following its activation by phosphatidylinositol-3,4,5-triphosphate-dependent Rac exchange factor 1 (PREX1). S1P has also been described to induce WPB exocytosis. Here, we confirm that S1P induces release of WPBs using von Willebrand factor (VWF) as a marker. Using siRNA mediated knockdown of gene expression we show that S1PR1 is not involved in S1P-mediated release of WPBs. In contrast depletion of the S1PR3 greatly reduced S1P-induced release of VWF. S1P-mediated enhancement of endothelial barrier function was not affected by S1PR3-depletion whereas it was greatly impaired in cells lacking S1PR1. The Rho kinase inhibitor Y27632 completely abrogated S1P-mediated release of VWF. Also, the calcium chelator BAPTA-AM significantly reduced S1P-induced release of VWF. Our findings indicate that S1P-induced release of haemostatic, inflammatory and angiogenic components stored within WPBs depends on the S1PR3.

Original languageEnglish
Article numbere91346
JournalPLoS ONE
Issue number3
Publication statusPublished - 14 Mar 2014
Externally publishedYes

Bibliographical note

This study was supported by grants from the Landsteiner Foundation for Blood Transfusion Research (LSBR 08.19, LSBR 12.44). RB was supported by a
European Hematology Association Research Fellowship. The funders had no role in study design, data collection and analysis, decision to publish, or preparation
of the manuscript.


Dive into the research topics of 'Sphingosine-1-phosphate receptor 3 mediates sphingosine-1-phosphate induced release of Weibel-Palade bodies from endothelial cells'. Together they form a unique fingerprint.

Cite this