Sphingosine-1-Phosphate and Its Receptors: A Mutual Link between Blood Coagulation and Inflammation

Figure 1

Synthesis of S1P and functions in the vascular system. De novo ceramide synthesis in general originates from condensation of serine, palmitoyl CoA, and fatty acid, a multistep enzyme catalysed process. Ceramide can be converted reversibly into sphingomyelin by sphingomyelinase or to glycosphingolipids. It is further metabolised by ceramidase to sphingosine, which can then be phosphorylated into S1P by sphingosine kinase isoforms 1 and 2 (SphK1/2). This phosphorylation can be reverted by the S1P phosphatases SPP1 and SPP2 or irreversible degradation by S1P lyase can occur. S1P may act intracellularly or is exported out of the cell via ABC transporters or Spns2, dependent on the cell type, and may bind to one of its receptors (S1PR1–S1PR5) to initiate G-protein mediated signaling. S1P modulates key processes of vascular pathogenesis which involve but are not restricted to modulation of cell proliferation and migration and regulation of vascular tone and immune functions.