Sphingolipidomics in Translational Sepsis Research-Biomedical Considerations and Perspectives.

Sphingolipids are a highly diverse group of lipids with respect to physicochemical properties controlling either structure, distribution, or function, all of them regulating cellular response in health and disease. Mass spectrometry, on the other hand, is an analytical technique characterizing ionized molecules or fragments thereof by mass-to-charge ratios, which has been prosperingly developed for rapid and reliable qualitative and quantitative identification of lipid species. Parallel to best performance of in-depth chromatographical separation of lipid classes, preconditions of precise quantitation of unique molecular species by preprocessing of biological samples have to be fulfilled.

Type 4 sphingosine 1-phosphate G protein-coupled receptor (S1P4) transduces S1P effects on T cell proliferation and cytokine secretion without signaling migration.

Sphingosine 1-phosphate (S1P) has diverse effects on T cells that are mediated by the predominant S1P1 and S1P4 G protein-coupled receptors (GPCRs). S1P4 is expressed principally by leukocytes, but little is known of its T cell effects in immunity. Two approaches were used to investigate S1P4 signals in T cells.

Physiological sphingosine 1-phosphate requirement for optimal activity of mouse CD4+ regulatory T Cells.

Sphingosine 1-phosphate (S1P) evokes T cell chemotaxis at 1-100 nM and inhibits chemotaxis to chemokines at 300 nM-1 uM through their predominant S1P1 G protein-coupled receptor (R). Mouse CD4+25+ regulatory T cells now are shown to express the same pattern of S1P1 > S1P4 >>other S1P Rs as other CD4 T cells. CD4+25+ T cell suppression of 3H-thymidine uptake and IL-2 generation by CD4+25- T cells stimulated with anti-T cell receptor antibodies without S1P was enhanced significantly by S1P at normal blood and lymph concentrations.

Transduction of multiple effects of sphingosine 1-phosphate (S1P) on T cell functions by the S1P1 G protein-coupled receptor.

Sphingosine 1-phosphate (S1P) in blood, lymph, and immune tissues stimulates and regulates T cell migration through their S1P(1) (endothelial differentiation gene encoded receptor-1) G protein-coupled receptors. We show now that S1P(1)Rs also mediate suppression of T cell proliferation and cytokine production. Uptake of [(3)H]thymidine by mouse CD4 T cells stimulated with anti-CD3 mAbs plus either anti-CD28 or IL-7 was inhibited up to 50% by 10(-9)-10(-6) M S1P.

Lysophospholipid growth factors and their G protein-coupled receptors in immunity, coronary artery disease, and cancer.

The physiological lysophospholipids (LPLs), exemplified by lysophosphatidic acid (LPA) and sphingosine 1-phosphate (S1P), are omnific mediators of normal cellular proliferation, survival, and functions. Although both LPA and S1P attain micromolar concentrations in many biological fluids, numerous aspects of their biosynthesis, transport, and metabolic degradation are unknown. Eight members of a new subfamily of G protein-coupled LPA/S1P receptors, originally termed Edg Rs, bind either LPA or S1P with high affinity and transduce a series of growth-related and/or cytoskeleton-based functional responses.