|
|
Blood, 1 April 2008, Vol. 111, No. 7, pp. 3489-3497.
Prepublished online as a Blood First Edition Paper on January 16, 2008; DOI 10.1182/blood-2007-05-092148.
 Previous Article | Next Article 
Submitted May 24, 2007
Accepted December 29, 2007
Basal and angiopoietin-1-mediated endothelial permeability is regulated by sphingosine kinase-1
Xiaochun Li, Milena Stankovic, Claudine S Bonder, Christopher N Hahn, Michelle Parsons, Stuart M Pitson, Pu Xia, Richard L Proia, Mathew A Vadas, and Jennifer R Gamble*
Division of Human Immunology, Hanson Institute, Institute of Medical & Veterinary Science, Adelaide, South Australia, Australia
Centenary Institute of Cancer Medicine & Cell Biology, The Medical Foundation and the University of Sydney, Sydney, NSW, Australia
Genetics of Development & Disease Branch, NIDDK, National Institutes of Health, Bethesda, MD, United States
* Corresponding author; email: j.gamble{at}centenary.org.au.
Endothelial cells (ECs) regulate the barrier function of blood vessels. Here we show that basal and angiopoietin-1 (Ang-1)-regulated control of EC permeability is mediated by two different functional states of sphingosine kinase-1 (SK-1). Mice depleted of SK-1 have increased vascular leakiness whereas mice transgenic for SK-1 in ECs show attenuation of leakiness. Furthermore, Ang-1 rapidly and transiently stimulates SK-1 activity and phosphorylation, and induces an increase in intracellular sphingosine-1-phosphate (S1P) concentration. Overexpression of SK-1 resulted in inhibition of permeability similar to that seen for Ang-1, whereas knockdown of SK-1 by siRNA blocked Ang-1-mediated inhibition of permeability. Transfection with SKS225A, a nonphosphorylatable mutant of SK-1, inhibited basal leakiness, and both SKS225A and a dominant-negative SK-1 mutant removed the capacity of Ang-1 to inhibit permeability. These effects were independent of extracellular S1P as knockdown or inhibition of S1P1, S1P2 or S1P3, did not affect the Ang-1 response. Thus, SK-1 levels in ECs powerfully regulate basal permeability in vitro and in vivo. In addition, the Ang-1-induced inhibition of leakiness is mediated through activation of SK-1, defining a new signaling pathway in the Ang-1 regulation of permeability.
 CiteULike  Connotea  Del.icio.us  Digg  Reddit  Technorati What's this?
This article has been cited by other articles:
|
|
|
|
 
N. Knezevic, M. Tauseef, T. Thennes, and D. Mehta
The G protein {beta}{gamma} subunit mediates reannealing of adherens junctions to reverse endothelial permeability increase by thrombin
J. Exp. Med.,
November 23, 2009;
206(12):
2761 - 2777.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. R. Gamble, W. Y. Sun, X. Li, C. N. Hahn, S. M. Pitson, M. A. Vadas, and C. S. Bonder
Sphingosine Kinase-1 Associates with Integrin {alpha}V{beta}3 to Mediate Endothelial Cell Survival
Am. J. Pathol.,
November 1, 2009;
175(5):
2217 - 2225.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J.-J. Liao, M.-C. Huang, K. Fast, K. Gundling, M. Yadav, J. R. Van Brocklyn, M. R. Wabl, and E. J. Goetzl
Immunosuppressive human anti-lymphocyte autoantibodies specific for the type 1 sphingosine 1-phosphate receptor
FASEB J,
June 1, 2009;
23(6):
1786 - 1796.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. S. Karliner
Sphingosine kinase regulation and cardioprotection
Cardiovasc Res,
May 1, 2009;
82(2):
184 - 192.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
F. Niessen, C. Furlan-Freguia, J. A. Fernandez, L. O. Mosnier, F. J. Castellino, H. Weiler, H. Rosen, J. H. Griffin, and W. Ruf
Endogenous EPCR/aPC-PAR1 signaling prevents inflammation-induced vascular leakage and lethality
Blood,
March 19, 2009;
113(12):
2859 - 2866.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
C. S. Bonder, W. Y. Sun, T. Matthews, C. Cassano, X. Li, H. S. Ramshaw, S. M. Pitson, A. F. Lopez, P. T. Coates, R. L. Proia, et al.
Sphingosine kinase regulates the rate of endothelial progenitor cell differentiation
Blood,
February 26, 2009;
113(9):
2108 - 2117.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
