Sources, metabolism, and regulation of circulating sphingosine-1-phosphate

Sphingosine-1-phosphate (S1P) is a bioactive sphingolipid that acts either as an intracellular messenger or as a ligand for its membrane receptors. S1P is a normal constituent of blood, where it is found both in plasma and blood cells. Compared with other cell types, sphingolipid metabolism in erythrocytes and platelets has unique features that allow the erythrocytes and platelets to accumulate S1P. In plasma, S1P is bound mainly to HDLs and albumin. Of note, metabolism and biological activity of S1P is to a large extent affected by the type of its carrier. Plasma S1P is characterized by a short half-life, indicating rapid clearance by degradative enzymes and the presence of high-capacity sources involved in maintaining its high concentration. These sources include blood cells, vascular endothelium, and hepatocytes. However, the extent to which each of these contributes to the plasma pool of S1P is a matter of debate. Circulating S1P plays a significant physiological role. It was found to be the key regulator of lymphocyte trafficking, endothelial barrier function, and vascular tone. The purpose of this review is to summarize the present state of knowledge on the metabolism, transport, and origin of plasma S1P, and to discuss the mechanisms regulating its homeostasis in blood.