Sphingosine kinase 1 and sphingosine-1-phosphate receptor 2 are vital to recovery from anaphylactic shock in mice

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Sphingosine kinase 1 and sphingosine-1-phosphate receptor 2 are vital to recovery from anaphylactic shock in mice.

Sphingosine kinase 1 (SphK1) and SphK2 are ubiquitous enzymes that generate sphingosine-1-phosphate (S1P), a ligand for a family of G protein-coupled receptors (S1PR1-S1PR5) with important functions in the vascular and immune systems. Here we explore the role of these kinases and receptors in recovery from anaphylaxis in mice. We found that Sphk2-/- mice had a rapid recovery from anaphylaxis. I...

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Sphingosine-1-phosphate receptor-2 protects against anaphylactic shock through suppression of eNOS in mice

Background: Sphingosine-1-phosphate receptor-2, S1P2, is expressed in vascular endothelial cells (EC). However, the role of S1P2 in vascular barrier integrity and anaphylaxis is not well understood. Endothelial nitric oxide (NO) synthase (eNOS) generates NO to mediate vascular leakage, compromising survival in anaphylaxis. We recently observed that endothelial S1P2 inhibits Akt, an activating k...

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Sphingosine Kinase 2 Inhibition and Blood Sphingosine 1-Phosphate Levels.

Sphingosine 1-phosphate (S1P) levels are significantly higher in blood and lymph than in tissues. This S1P concentration difference is necessary for proper lymphocyte egress from secondary lymphoid tissue and to maintain endothelial barrier integrity. Studies with mice lacking either sphingosine kinase (SphK) type 1 and 2 indicate that these enzymes are the sole biosynthetic source of S1P, but ...

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Sphingosine kinase type 2 inhibition elevates circulating sphingosine 1-phosphate.

S1P (sphingosine 1-phosphate) is a pleiotropic lipid mediator involved in numerous cellular and physiological functions. Of note among these are cell survival and migration, as well as lymphocyte trafficking. S1P, which exerts its effects via five GPCRs (G-protein-coupled receptors) (S1P1-S1P5), is formed by the action of two SphKs (sphingosine kinases). Although SphK1 is the more intensively s...

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Tumor-suppressive sphingosine-1-phosphate receptor-2 counteracting tumor-promoting sphingosine-1-phosphate receptor-1 and sphingosine kinase 1 - Jekyll Hidden behind Hyde.

Sphingosine-1-phosphate (S1P) is a plasma lipid mediator with multiple roles in mammalian development, physiology and pathophysiology. It is constitutively produced mostly by erythrocytes by the action of sphingosine kinase 1 (SphK1), resulting in high (∼0.5 micromolar) steady-state plasma S1P content and steep S1P concentration gradient imposed between plasma/lymph/tissue interstitial fluid. S...

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ژورنال

عنوان ژورنال: Journal of Clinical Investigation

سال: 2010

ISSN: 0021-9738

DOI: 10.1172/jci40659