Abstract
Following the discovery of an immunosuppressive substance isolated from one of the entomopathogenic fungi 'vegetable wasps and plant worms', FTY720, whose immunosuppressive action is more potent than that of cyclosporin, was developed. In contrast to classical immunosuppressants such as cyclosporin, FTY720 does not affect the growth, maturation and activation of lymphocytes, but causes a reduction in the number of circulating lymphocytes as a result of enhanced homing of lymphocytes to the secondary lymphoid organs. It has recently been reported that FTY720 is phosphorylated in vivo by sphingosine kinase, and the phosphorylated FTY720 is a ligand of the receptors of sphingosine 1-phosphate (SIP), which are G-protein-coupled receptors. SIP has been recognized most prominently as a platelet-derived lipid mediator which regulates several functions of endothelial and smooth muscle cells. In addition, recent studies have suggested the crucial roles for SIP in immunological, and inflammatory modulation.
