Induction and suppression of endothelial cell apoptosis by sphingolipids: A possible in vitro model for cell-cell interactions between platelets and endothelial cells

Because sphingosine (Sph) is actively incorporated into platelets and rapid ly converted to sphingosine 1-phosphate (Sph-1-P), which is then released e xtracellularly, it is important to study the effects of Sph and Sph-1-P on endothelial cells from the viewpoint of platelet-endothelial cell interacti on. In this study, we found that Sph, as well as ceramide, induces apoptosi s in human umbilical vein endothelial cells (HUVECs). In contrast, Sph-1-P acts as a HUVEC survival factor; this bioactive lipid was shown to protect HUVECs from apoptosis induced by the withdrawal of growth factors and to st imulate HUVEC DNA synthesis. In metabolic studies, [H-3]Sph, incorporated i nto HUVECs, was converted to [H-3]Cer and further to [H-3]sphingomyelin in a time-dependent manner, whereas [H-3]Sph-1-P formation from [H-3]Sph was w eak and transient. These findings in HUVECs are very different from those o f platelets, which possess a highly active Sph kinase but lack Sph-1-P lyas e. As a result, platelets abundantly store Sph-1-P, whereas HUVECs contain much less Sph-1-P. Finally, HUVECs, in contrast to platelets, failed to rel ease Sph-1-P extracellularly, indicating that HUVECs themselves are not abl e to supply the survival factor Sph-1-P, but receive it from activated plat elets. Our results suggest that platelets may maintain the integrity of end othelial cells by incorporating Sph and releasing Sph-1-P, (C) 1999 by The American Society of Hematology.