Sphingosine 1-phosphate promotes endothelial cell barrier integrity by Edg-dependent cytoskeletal rearrangement

Joe G.N. Garcia, Feng Liu, Alexander Dmitriyevich Verin, Anna Birukova, Melissa A. Dechert, William T. Gerthoffer, James R. Bamburg, Denis English

Research output: Contribution to journalArticle

642 Citations (Scopus)

Abstract

Substances released by platelets during blood clotting are essential participants in events that link hemostasis and angiogenesis and ensure adequate wound healing and tissue injury repair. We assessed the participation of sphingosine 1-phosphate (Sph-1-P), a biologically active phosphorylated lipid growth factor released from activated platelets, in the regulation of endothelial monolayer barrier integrity, which is key to both angiogenesis and vascular homeostasis. Sph-1-P produced rapid, sustained, and dose-dependent increases in transmonolayer electrical resistance (TER) across both human and bovine pulmonary artery and lung microvascular endothelial cells. This substance also reversed barrier dysfunction elicited by the edemagenic agent thrombin. Sph-1-P-mediated barrier enhancement was dependent upon G-receptor coupling to specific members of the endothelial differentiation gene (Edg) family of receptors (Edg-1 and Edg-3), Rho kinase and tyrosine kinase-dependent activation, and actin filament rearrangement. Sph-1-P-enhanced TER occurred in conjunction with Rac GTPase- and p21-associated kinase-dependent endothelial cortical actin assembly with recruitment of the actin filament regulatory protein, cofilin. Platelet-released Sph-1-P, linked to Rac- and Rho-dependent cytoskeletal rearrangement, may act late in angiogenesis to stabilize newly formed vessels, which often display abnormally increased vascular permeability.

Original languageEnglish (US)
Pages (from-to)689-701
Number of pages13
JournalJournal of Clinical Investigation
Volume108
Issue number5
DOIs
StatePublished - Jan 1 2001
Externally publishedYes

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Endothelial Cells
Blood Platelets
Genes
Electric Impedance
Actin Cytoskeleton
Actin Depolymerizing Factors
rho-Associated Kinases
GTP Phosphohydrolases
Capillary Permeability
Blood Coagulation
Hemostasis
Thrombin
Protein-Tyrosine Kinases
Wound Healing
Pulmonary Artery
Blood Vessels
Actins
Intercellular Signaling Peptides and Proteins
Homeostasis
Phosphotransferases

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Sphingosine 1-phosphate promotes endothelial cell barrier integrity by Edg-dependent cytoskeletal rearrangement. / Garcia, Joe G.N.; Liu, Feng; Verin, Alexander Dmitriyevich; Birukova, Anna; Dechert, Melissa A.; Gerthoffer, William T.; Bamburg, James R.; English, Denis.

In: Journal of Clinical Investigation, Vol. 108, No. 5, 01.01.2001, p. 689-701.

Research output: Contribution to journalArticle

Garcia, JGN, Liu, F, Verin, AD, Birukova, A, Dechert, MA, Gerthoffer, WT, Bamburg, JR & English, D 2001, 'Sphingosine 1-phosphate promotes endothelial cell barrier integrity by Edg-dependent cytoskeletal rearrangement', Journal of Clinical Investigation, vol. 108, no. 5, pp. 689-701. https://doi.org/10.1172/JCI12450
Garcia, Joe G.N. ; Liu, Feng ; Verin, Alexander Dmitriyevich ; Birukova, Anna ; Dechert, Melissa A. ; Gerthoffer, William T. ; Bamburg, James R. ; English, Denis. / Sphingosine 1-phosphate promotes endothelial cell barrier integrity by Edg-dependent cytoskeletal rearrangement. In: Journal of Clinical Investigation. 2001 ; Vol. 108, No. 5. pp. 689-701.
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