Sphingosine 1-phosphate as an intracellular messenger and extracellular mediator in immunity.

Unlabelled: The omnific mediator system composed of sphingosine 1-phosphate (S1P) and its five G-protein-coupled receptors, designated S1P(1)-S1P(5), affects diverse cellular functions in the nervous, endocrine, cardiovascular and immune systems. The many activities of the S1P-S1P(1) axis, which predominates in the cardiovascular and immune systems, have previously been classified according to their relationship with the distinct functional roles of each type of cell or according to their most frequently used signalling pathways. In the immune system, cell surface S1P(1) receptors transduce the rapid, transient effects of extracellular S1P on T- and B-lymphocyte trafficking in the lymphoid system, lymphocyte migration in non-immune tissues and cytokine generation.

Sphingosine 1-phosphate and its G protein-coupled receptors constitute a multifunctional immunoregulatory system.

The lysophospholipid growth factors sphingosine 1-phosphate (S1P) and lysophosphatidic acid (LPA) are generated by many cells involved in immunity, including macrophages, dendritic cells, mast cells, and platelets, with resultant lymph and plasma concentrations of 0.1-1 microM. All immune cells express distinctive profiles of G protein-coupled receptors (GPCRs) for S1P and LPA, which are regulated developmentally and by cellular activation.

Embryonic brain expression analysis of lysophospholipid receptor genes suggests roles for s1p(1) in neurogenesis and s1p(1-3) in angiogenesis.

In a comparison of embryonic brain expression patterns of lysophosphatidic acid and sphingosine 1-phosphate receptor genes (lpa(1-3) and s1p(1-5), respectively), transcripts detected by Northern blot were subsequently localized using in situ hybridization. We found striking s1p(1) expression adjacent to several ventricles. Near the lateral ventricle, s1p(1) expression was temporally and spatially coincident with neurogenesis and overlapped with lpa(1) in the neocortical area.