Am J Clin Exp Immunol 2012;1(2):90-100

Review Article
The role of sphingosine 1-phosphate in immunity and sepsis

Markus H Gräler

Molecular Cancer Research Centre, Charité University Medical School, Augustenburger Platz 1, 13353 Berlin, Germany

Received June 28, 2012; Accepted August 23, 2012; Epub September 27, 2012; Published November 30, 2012

Abstract: Sphingosine 1-phosphate (S1P) is a lipid metabolite with intra- and extracellular signalling properties.
It activates five G protein-coupled cell surface receptors designated S1P-receptors type 1-5 (S1P1-5) that transmit
extracellular signals into cells, and it modulates intracellular signalling as a cofactor. The analysis of sphingosine
kinases (SphK) type 1 and 2, the key enzymes for S1P production, in different infection models point to an important
role for the activation of different immune cells like macrophages, mast cells, and dendritic cells. S1P additionally
influences local and systemic lymphocyte circulation and positioning, the vascular tone, and blood pressure. Modulation
of S1P-mediated signalling pathways therefore results either in local immune cell activation or systemic immune
suppression, or both. Pharmacological approaches that modulate certain S1P-mediated signalling pathways
while leaving others untouched appear to be promising new avenues for next generation pharmaceuticals. This review
summarizes current strategies to modulate S1P signalling for immune intervention with the clear focus on the
specificity of the different principles applied. Known local and systemic effects of S1P on immunity are discussed as
potential pharmaceutical targets to combat immune and autoimmune diseases and sepsis. (AJCEI1206001).

Keywords: Lymphocyte egress, sphingosine kinase, S1P-lyase, sphingolipid metabolism, lymphopenia, FTY720,
rheumatoid arthritis, multiple sclerosis, asthma, anaphylaxis

Address all correspondence to:
Dr. Markus Gräler,
Molecular Cancer Research Centre (MKFZ)
Charité University Medical School (CVK)
Augustenburger Platz 1, Forum 4, 13353 Berlin, Germany.
Phone: +49-30-450 559 106; Fax: +49-30-450 559 975
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