Role of sphingosine-1 phosphate in the enhancement of endothelial barrier integrity by platelet-released products

Kane L. Schaphorst, Eddie Chiang, Keri N. Jacobs, Ari Zaiman, Viswanathan Natarajan, Frederick Wigley, Joe G.N. Garcia

Research output: Contribution to journalArticle

Abstract

In vitro and in vivo evidence indicates that circulating platelets affect both vascular integrity and hemostasis. How platelets enhance the permeability barrier of the vascular endothelium is not well understood. We measured the effect of isolated human platelets on human pulmonary artery endothelial cell (EC) barrier integrity by monitoring transmonolayer electrical resistance. EC barrier function was significantly increased by the addition of platelets (∼40% maximum, 2.5 × 106 platelets/ml). Platelet supernatants, derived from 2.5 × 106 platelets/ml, reproduced the barrier enhancement and reversed the barrier dysfunction produced by the edemagenic agonist thrombin, which implicates a soluble barrier-promoting factor. The barrier-enhancing effect of platelet supernatants was heat stable but was attenuated by either charcoal delipidation (suggesting a vasoactive lipid mediator) or pertussis toxin, implying involvement of a Giα-coupled receptor signal transduction pathway. Sphingosine-1-phosphate (S1P), a sphingolipid that is released from activated platelets, is known to ligate G protein-coupled EC differentiation gene (EDG) receptors, increase EC electrical resistance, and reorganize the actin cytoskeleton (Garcia JG, Liu F, Verin AD, Birukova A, Dechert MA, Gerthoffer WT, Bamberg JR, and English D. J Clin Invest 108: 689-701, 2001). Infection of EC with an adenoviral vector expressing an antisense oligonucleotide directed against EDG-1 but not infection with control vector attenuated the barrier-enhancing effect of both platelet supernatants and S1P. These results indicate that a major physiologically relevant vascular barrier-protective mediator produced by human platelets is S1P.

Original languageEnglish (US)
Pages (from-to)L258-L267
JournalAmerican Journal of Physiology - Lung Cellular and Molecular Physiology
Volume285
Issue number1 29-1
DOIs
StatePublished - Jul 1 2003

Keywords

  • Cell differentiating gene
  • Differentiation
  • Endothelium
  • G protein
  • Injury
  • Lung
  • Vasculature

ASJC Scopus subject areas

  • Physiology
  • Pulmonary and Respiratory Medicine
  • Physiology (medical)
  • Cell Biology

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