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Seminars in Immunopathology

Erschienen in:

01.01.2012 | Review

Sphingosine 1-phosphate in coagulation and inflammation

verfasst von: Hideru Obinata, Timothy Hla

Erschienen in: Seminars in Immunopathology | Ausgabe 1/2012

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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, S1P_1–5, 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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Titel: Sphingosine 1-phosphate in coagulation and inflammation
verfasst von: Hideru Obinata
Timothy Hla
Publikationsdatum: 01.01.2012
Verlag: Springer-Verlag
Erschienen in: Seminars in Immunopathology / Ausgabe 1/2012
Print ISSN: 1863-2297
Elektronische ISSN: 1863-2300
DOI: https://doi.org/10.1007/s00281-011-0287-3

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