Sphingosine 1-Phosphate, a Bioactive Sphingolipid Abundantly Stored in Platelets, Is a Normal Constituent of Human Plasma and Serum

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Abstract
Although sphingosine 1-phosphate (Sph-l-P) is reportedly involved in diverse cellular processes and the physiological roles of this bioactive sphingolipid have been strongly suggested, few studies have revealed the presence of Sph-l-P in human samples, including body fluids and cells, under physiological conditions. In this study, we identified Sph-l-P as a normal constituent of human plasma and serum. The Sph-l-P levels in plasma and serum were 191±79 and 484±82 pmol/ml (mean±SD, n=8), respectively. Furthermore, when Sph-l-P was measured in paired plasma and serum samples obtained from 6 healthy adults, the serum Sph-1-P/plasma Sph-l-P ratio was found to be 2.65±1.26 (mean±SD). It is most likely that the source of discharged Sph-l-P during blood clotting is platelets, because platelets abundantly store Sph-l-P compared with other blood cells, and release part of their stored Sph-l-P extracellularly upon stimulation. We also studied Sph-l-P-related metabolism in plasma. [3H]Sph was stable and not metabolized at all in plasma, but was rapidly incorporated into platelets and metabolized mainly to Sph-l-P in platelet-rich plasma. [3H]Sph-l-P was found to be unchanged in plasma, revealing that plasma does not contain the enzymes needed for Sph-l-P degradation. In summary, platelets can convert Sph into Sph-l-P, and are storage sites for the latter in the blood. In view of the diverse biological effects of Sph-l-P, the release of Sph-l-P from activated platelets may be involved in a variety of physiological and pathophysiological processes, including thrombosis, hemostasis, atherosclerosis and wound healing.

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