Sphingosine-1-phosphate modulation of basal permeability and acute inflammatory responses in rat venular microvessels

Roger H. Adamson, Rupinder K. Sarai, Ariungerel Altangerel, Twanda L. Thirkill, Joyce F. Clark, Fitz Roy E Curry

Research output: Contribution to journalArticle

41 Scopus citations

Abstract

Aims Although several cultured endothelial cell studies indicate that sphingosine-1-phosphate (S1P), via GTPase Rac1 activation, enhances endothelial barriers, very few in situ studies have been published. We aimed to further investigate the mechanisms whereby S1P modulates both baseline and increased permeability in intact microvessels. Methods and resultsWe measured attenuation by S1P of platelet-activating factor (PAF)-or bradykinin (Bk)-induced hydraulic conductivity (Lp) increase in mesenteric microvessels of anaesthetized rats. S1P alone (1-5 M) attenuated by 70 the acute Lp increase due to PAF or Bk. Immunofluorescence methods in the same vessels under identical experimental conditions showed that Bk or PAF stimulated the loss of peripheral endothelial cortactin and rearrangement of VE-cadherin and occludin. Our results are the first to show in intact vessels that S1P pre-treatment inhibited rearrangement of VE-cadherin and occludin induced by PAF or Bk and preserved peripheral cortactin. S1P (1-5 M, 30 min) did not increase baseline Lp. However, 10 M S1P (60 min) increased Lp two-fold.Conclusion Our results conform to the hypothesis that S1P inhibits acute permeability increase in association with enhanced stabilization of peripheral endothelial adhesion proteins. These results support the idea that S1P can be useful to attenuate inflammation by enhancing endothelial adhesion through activation of Rac-dependent pathways.

Original languageEnglish (US)
Pages (from-to)344-351
Number of pages8
JournalCardiovascular Research
Volume88
Issue number2
DOIs
StatePublished - Nov 1 2010

Keywords

  • cAMP
  • Capillary permeability
  • Inflammation
  • Rac1
  • Rap1

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)
  • Physiology

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    Adamson, R. H., Sarai, R. K., Altangerel, A., Thirkill, T. L., Clark, J. F., & Curry, F. R. E. (2010). Sphingosine-1-phosphate modulation of basal permeability and acute inflammatory responses in rat venular microvessels. Cardiovascular Research, 88(2), 344-351. https://doi.org/10.1093/cvr/cvq184