Sphingosine 1-phosphate in blood: function, metabolism, and fate

Sphingosine 1-phosphate (S1P) is a lipid metabolite and a ligand of five G protein-coupled cell surface receptors S1PR1 to S1PR5. These receptors are expressed on various cells and cell types of the immune, cardiovascular, respiratory, hepatic, reproductive, and neurologic systems, and S1P has an impact on many different pathophysiological conditions including autoimmune, cardiovascular, and neurodegenerative diseases, cancer, deafness, osteogenesis, and reproduction. While these diverse signalling properties of S1P have been extensively reviewed, the particular role of S1P in blood is still a matter of debate. Blood contains the highest S1P concentration of all body compartments, and several questions are still not sufficiently answered: Where does it come from and how is it metabolized? Why is the concentration of S1P in blood so high? Are minor changes of the high blood S1P concentrations physiologically relevant? Do blood cells and vascular endothelial cells that are constantly exposed to high blood S1P levels still respond to S1P via S1P receptors? Recent data reveal new insights into the functional role and the metabolic fate of blood-borne S1P. This review aims to summarize our current knowledge regarding the source, secretion, transportation, function, metabolism, and fate of S1P in blood.