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Sphingosine 1-phosphate in coagulation and inflammation

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Abstract

Sphingosine 1-phosphate (S1P) is a lipid mediator produced from sphingomyelin by the sequential enzymatic actions of sphingomyelinase, ceramidase, and sphingosine kinase. Five subtypes of cell surface G-protein-coupled receptors, S1P1–5, mediate the actions of S1P in various organs systems, most notably cardiovascular, immune, and central nervous systems. S1P is enriched in blood and lymph but is present at much lower concentrations in interstitial fluids of tissues. This vascular S1P gradient is important for the regulation of trafficking of various immune cells. FTY720, which was recently approved for the treatment of relapsing-remitting multiple sclerosis, potently sequesters lymphocytes into lymph nodes by functionally antagonizing the activity of the S1P1 receptor. S1P also plays critical roles in the vascular barrier integrity, thereby regulating inflammation, tumor metastasis, angiogenesis, and atherosclerosis. Recent studies have also revealed the involvement of S1P signaling in coagulation and in tumor necrosis factor α-mediated signaling. This review highlights the importance of S1P signaling in these inflammatory processes as well as the contribution of each receptor subtype, which exhibits both cooperative and redundant functions.

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Acknowledgments

This work was supported by NIH grants HL-67330 and HL-89934.

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Authors and Affiliations

  1. Center for Vascular Biology, Department of Pathology and Laboratory Medicine, Weill Cornell Medical College, Cornell University, 1300 York Avenue, New York, NY, 10065, USA

    Hideru Obinata & Timothy Hla

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  1. Hideru Obinata
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  2. Timothy Hla
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Correspondence to Timothy Hla.

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This article is published as part of the Special Issue on Coagulation & Inflammation [34:1].

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Obinata, H., Hla, T. Sphingosine 1-phosphate in coagulation and inflammation. Semin Immunopathol 34, 73–91 (2012). https://doi.org/10.1007/s00281-011-0287-3

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  • DOI: https://doi.org/10.1007/s00281-011-0287-3

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