1. Sphingolipids are potent second messengers modulating
biochemical intracellular events and acting as ligands to
mediate extracellular systems. Sphingosine kinase (SPHK) is
the enzyme that phosphorylates sphingosine into sphingosine-
1-phosphate (S1P), a potent bioactive sphingolipid.
2. The fact that SPHK is highly conserved from protozoa to
mammals and is ubiquitous in living tissues reveals important
roles of the SPHK pathway for the maintenance of health
maintenance. This is also supported by comprehensive reviews
on features of its main product, S1P, as having intracellular as
well as extracellular roles, inducing a wide range of physiological
responses from triggering Ca2+ release from internal
stores to promoting growth and cell motility.
3. Immune cell activities have been shown to be modulated
by the dynamic balance between ceramide, sphingosine and
S1P, conceptualized as a rheostat. Cell proliferation, differentiation,
motility and survival have been attributed to the
regulatory actions of S1P. The properties of SPHK activity in
immune cells are linked to the functions of triggered growth
and survival factors, phorbol esters, hormones, cytokines and
chemokines, as well as antigen receptors, such as Fc y
RI and FceRI.
4. Mechanisms of the SPHK signalling pathway are
explored as new targets for drug development to suppress
inflammation and other pathological conditions.
Key words: immune cells, inflammation, lymphocytes,
mast cells, monocytes/ macrophages, neutrophils, signalling,
sphingosine kinase, sphingosine-1-phosphate.
ArtÃculo publicado en Clinical and Experimental Pharmacology and Physiology.(2005) 32, 153-161.