HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: 293/4/C1309    most recent 00014.2007v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Web of Science (11) Citing Articles via Google Scholar Google Scholar Articles by Xu, M. Articles by Minnear, F. L. Search for Related Content PubMed PubMed Citation Articles by Xu, M. Articles by Minnear, F. L.

VASCULAR BIOLOGY

Sphingosine 1-phosphate rapidly increases endothelial barrier function independently of VE-cadherin but requires cell spreading and Rho kinase

¹Center for Interdisciplinary Research in Cardiovascular Sciences, ²Department of Physiology and Pharmacology, and ³Department of Neurobiology and Anatomy, West Virginia University School of Medicine, Morgantown, West Virginia; and ⁴Center for Cardiovascular Sciences, Albany Medical College, Albany, New York

Submitted 10 January 2007 ; accepted in final form 13 July 2007

Sphingosine 1-phosphate (S1P) rapidly increases endothelial barrier function and induces the assembly of the adherens junction proteins vascular endothelial (VE)-cadherin and catenins. Since VE-cadherin contributes to the stabilization of the endothelial barrier, we determined whether the rapid, barrier-enhancing activity of S1P requires VE-cadherin. Ca²⁺-dependent, homophilic VE-cadherin binding of endothelial cells, derived from human umbilical veins and grown as monolayers, was disrupted with EGTA, an antibody to the extracellular domain of VE-cadherin, or gene silencing of VE-cadherin with small interfering RNA. All three protocols caused a reduction in the immunofluorescent localization of VE-cadherin at intercellular junctions, the separation of adjacent cells, and a decrease in basal endothelial electrical resistance. In all three conditions, S1P rapidly increased endothelial electrical resistance. These findings demonstrate that S1P enhances the endothelial barrier independently of homophilic VE-cadherin binding. Junctional localization of VE-cadherin, however, was associated with the sustained activity of S1P. Imaging with phase-contrast and differential interference contrast optics revealed that S1P induced cell spreading and closure of intercellular gaps. Pretreatment with latrunculin B, an inhibitor of actin polymerization, or Y-27632, a Rho kinase inhibitor, attenuated cell spreading and the rapid increase in electrical resistance induced by S1P. We conclude that S1P rapidly closes intercellular gaps, resulting in an increased electrical resistance across endothelial cell monolayers, via cell spreading and Rho kinase and independently of VE-cadherin.

permeability; microscopy; electric cell-substrate impedance sensing; human umbilical vein endothelial cell

This article has been cited by other articles:

				K. Sattler and B. Levkau Sphingosine-1-phosphate as a mediator of high-density lipoprotein effects in cardiovascular protection Cardiovasc Res, May 1, 2009; 82(2): 201 - 211. [Abstract] [Full Text] [PDF]

				M. Guo, J. W. Breslin, M. H. Wu, C. J. Gottardi, and S. Y. Yuan VE-cadherin and {beta}-catenin binding dynamics during histamine-induced endothelial hyperpermeability Am J Physiol Cell Physiol, April 1, 2008; 294(4): C977 - C984. [Abstract] [Full Text] [PDF]

				D. Vestweber VE-Cadherin: The Major Endothelial Adhesion Molecule Controlling Cellular Junctions and Blood Vessel Formation Arterioscler Thromb Vasc Biol, February 1, 2008; 28(2): 223 - 232. [Abstract] [Full Text] [PDF]