Sphingosine 1-phosphate is a blood constituent released from activated platelets, possibly playing a variety of physiological and pathophysiological roles.

Abstract

We have found that sphingosine 1-phosphate (Sph-1-P) acts as an autocrine stimulator of platelets, being abundantly stored in platelets and released extracellularly, and that its exogenous addition induces platelet activation (Yatomi et al., Blood 1995, 86, 193-202) through a specific receptor on the platelet surface (Yatomi et al., J. Biol. Chem. 1997, 272, 5291-5297). Very recently, we identified Sph-1-P as a normal constituent of human plasma and serum. Sph-1-P levels in plasma and serum were 191+/-79 and 484+/-82 pmol/ml (mean +/- S.D., n = 8), respectively. Platelets are most likely the source of Sph-1-P discharged during blood clotting, since they abundantly store Sph-1-P as compared with other blood cells, and release considerable amounts of stored Sph-1-P extracellularly upon stimulation. The Sph-1-P released from activated platelets may be involved in a variety of physiological processes, including thrombosis, atherosclerosis, and wound healing. Moreover, we often observed that Sph-1-P injection into mice (iv., 10 mg/kg) caused immediate rigor and death. This may be related to the recent observations from an other laboratory that nanomolar concentrations of Sph-1-P affected atrial myocyte K+ channel. These observations taken together strongly suggest pathophysiological roles of the released Sph-1-P in the blood. As one example, we found that Sph-1-P content in the plasma of platelet concentrates correlated with poor platelet increments after transfusion and with the occurrence of transfusion reactions in patients.