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Sphingosine-1-phosphate: a platelet-activating sphingolipid released from
agonist-stimulated human platelets
Y Yatomi, F Ruan, S Hakomori and Y Igarashi
Biomembrane Institute, University of Washington, Seattle 98119, USA.
Sphingosine-1-phosphate (Sph-1-P) is the initial product of catabolism of
sphingosine by sphingosine kinase and is cleaved by Sph-1-P lyase to a
fatty aldehyde and ethanolamine phosphate. This phosphorylated sphingoid
base is not only an intermediary catabolite, but also a bioactive lipid
with important functions, including stimulation of cell proliferation in
Swiss 3T3 fibroblasts and inhibition of tumor cell motility. In the present
study, we examined functional roles of Sph-1-P in human platelets. Sph-1-P
induced platelet shape change and aggregation reactions, although it failed
to elicit secretion. Sphingosine, ceramide, sphingomyelin, and
N,N-dimethylsphingosine did not mimic the positive effects of Sph-1-P on
platelets. Subthreshold concentrations of Sph-1-P and weak platelet
agonists such as adenosine diphosphate (ADP) and epinephrine
synergistically elicited aggregation, which may be important for efficient
amplification of platelet activation. Sph-1-P induced intracellular Ca2+
mobilization and the dose-response for Ca2+ release correlated closely with
the concentration required for induction of shape change. On addition of
[3H]sphingosine to intact platelets, the label was rapidly converted to
Sph-1-P, and subsequently to ceramide and sphingomyelin. Interestingly, the
Sph-1-P formed was specifically released into medium on stimulation of
platelets with physiologic agonists. The amount of Sph-1-P in platelets, as
measured by its conversion into radiolabeled N-acetyl-Sph- 1-P, was 1.4
nmol/10(9) cells and was about four times higher than the mass of Sph
present. When compared by mole percent Sph-1- P/phospholipid, the value for
platelets is over 10 times higher than that for neutrophils. Our results
suggest that Sph-1-P, rapidly converted from sphingosine, abundantly stored
in platelets, and released on the cell activation, may play a physiologic
role in thrombosis, hemostasis, and the natural wound-healing processes.
Volume 86,
Issue 1,
pp. 193-202,
07/01/1995
Copyright © 1995 by The American Society of Hematology
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