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Blood, 15 November 2000, Vol. 96, No. 10, pp. 3431-3438

HEMOSTASIS, THROMBOSIS, AND VASCULAR BIOLOGY

Sphingosine 1-phosphate as a major bioactive lysophospholipid that is released from platelets and interacts with endothelial cells

Yutaka Yatomi, Tsukasa Ohmori, Ge Rile, Fuminori Kazama, Hirotaka Okamoto, Takamitsu Sano, Kaneo Satoh, Shoji Kume, Gabor Tigyi, Yasuyuki Igarashi, and Yukio Ozaki

From the Department of Laboratory Medicine, Yamanashi Medical University, Nakakoma, Japan; the Department of Biomembrane and Biofunctional Chemistry, Graduate School of Pharmaceutical Sciences, Hokkaido University, Sapporo, Japan; and the Department of Physiology, University of Tennessee Health Science Center, Memphis, TN.

The serum-borne lysophospholipid mediators sphingosine 1-phosphate (Sph-1-P) and lysophosphatidic acid (LPA) have been shown to be released from activated platelets and to act on endothelial cells. In this study, we employed the repeated lipid extraction (under alkaline and acidic conditions), capable of detecting Sph-1-P, LPA, and possibly structurally similar lysophospholipids, whereby a marked formation of [32P]Sph-1-P, but not [32P]LPA, was observed in [32P]orthophosphate-labeled platelets. Platelet Sph-1-P release, possibly mediated by protein kinase C, was greatly enhanced in the presence of albumin, which formed a complex with Sph-1-P. This finding suggests that platelet Sph-1-P may become accessible to depletion by albumin when its transbilayer movement (flipping) across the plasma membrane is enhanced by protein kinase C. Although human umbilical vein endothelial cells expressed receptors for both Sph-1-P and LPA, Sph-1-P acted much more potently than LPA on the cells in terms of intracellular Ca++ mobilization, cytoskeletal reorganization, and migration. The results suggest that Sph-1-P, rather than LPA, is a major bioactive lysophospholipid that is released from platelets and interacts with endothelial cells, under the conditions in which critical platelet-endothelial interactions (including thrombosis, angiogenesis, and atherosclerosis) occur. Furthermore, albumin-bound Sph-1-P may account for at least some of the serum biological activities on endothelial cells, which have been ascribed to the effects of albumin-bound LPA, based on the similarities between LPA and serum effects.

© 2000 by The American Society of Hematology.
 

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