Metabolism and functional effects of sphingolipids in blood cells

We examined the sphingolipid metabolism of peripheral blood cells, i. e. platelets, erythrocytes, neutrophils and mononuclear cells. A distinguishing characteristic of sphingolipid metabolism in these highly differentiated cells was their high sphingosine (Sph) kinase activity. The occurrence of [3H]sphingosine 1-phosphate (Sph-1-P) from [3H]Sph (actively incorporated from the outside) in the blood cells was strong, long-lasting, and independent of cell activation. Hence, the possibility of Sph-1-P playing a second messenger role is remote in these cells. About 40% of platelet Sph-1-P could be released extracellularly by 12-O-tetradecanoylphorbol 13-acetate, possibly through mediation by protein kinase C. On the other hand, in erythrocytes, neutrophils and mononuclear cells a significant percentage of Sph-1-P formed inside the cell was discharged without stimulation, whereas the stimulation-dependent release was marginal. In contrast to active [3H]Sph conversion to [3H]Sph-1-P, formation of [3H]sphingomyelin was barely detectable in the blood cells; this was especially true for anucleate platelets and erythrocytes. The Sph --> Sph-1-P pathway may become predominant over the Sph --> Cer --> sphingomyelin pathway during late-stage differentiation into platelets or erythrocytes. Sph and its methylated derivative, N, N-dimethylsphingosine, induced apoptosis not only in neutrophils but also in mononuclear cells, whereas Sph-1-P elicited Ca2+ mobilization in platelets. Our results suggest that all blood cells may remove plasma Sph, which is harmful or suppressive to cellular functions, and change it into Sph-1-P, acting as the source of plasma Sph-1-P, which may play a variety of important roles in blood vessels.