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Sphingosine-1-phosphate and other lipid mediators generated by mast cells as
critical players in allergy and mast cell function
#MMPMID25941085
Kulinski JM
; Muņoz-Cano R
; Olivera A
Eur J Pharmacol
2016[May]; 778
(?): 56-67
PMID25941085
show ga
Sphingosine-1-phosphate (S1P), platelet activating factor (PAF) and eicosanoids
are bioactive lipid mediators abundantly produced by antigen-stimulated mast
cells that exert their function mostly through specific cell surface receptors.
Although it has long been recognized that some of these bioactive lipids are
potent regulators of allergic diseases, their exact contributions to disease
pathology have been obscured by the complexity of their mode of action and the
regulation of their metabolism. Indeed, the effects of such lipids are usually
mediated by multiple receptor subtypes that may differ in their signaling
mechanisms and functions. In addition, their actions may be elicited by cell
surface receptor-independent mechanisms. Furthermore, these lipids may be
converted into metabolites that exhibit different functionalities, adding another
layer of complexity to their overall biological responses. In some instances, a
second wave of lipid mediator synthesis by both mast cell and non-mast cell
sources may occur late during inflammation, bringing about additional roles in
the altered environment. New evidence also suggests that bioactive lipids in the
local environment can fine-tune mast cell maturation and phenotype, and thus
their responsiveness. A better understanding of the subtleties of the
spatiotemporal regulation of these lipid mediators, their receptors and functions
may aid in the pursuit of pharmacological applications for allergy treatments.
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