Sphingosine-1-phosphate and other lipid mediators generated by mast cells as critical players in allergy and mast cell function

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 bioacti...

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Published inEuropean journal of pharmacology Vol. 778; pp. 56 - 67
Main Authors Kulinski, Joseph M., Muñoz-Cano, Rosa, Olivera, Ana
Format Journal Article
LanguageEnglish
Published Netherlands Elsevier B.V 05.05.2016
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Abstract 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.
AbstractList Sphingosine-1phosphate (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.
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.
Author Olivera, Ana
Kulinski, Joseph M.
Muñoz-Cano, Rosa
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Keywords PGD2
NO
Allergy
eNOS
5-LO
SphK
Eicosanoids
Prostaglandin E2 (CID: 5280360)
Cys-LT
LTC4S
TNF
RBL-2H3
Prostaglandin D2 (CID: 448457)
S1P
PI3K
Platelet activating factor (CID: 108156)
Sphingosine-1-phosphate
LTB4
S1P1–5
FTY720 (CID: 107969)
AA
PGE2
ABCC1
PGDS
PLA2
DP1-2
TRAF2
COX
Platelet activating factor
PAF
KIT
SCF
BLT1-2
GPCR
FcεRI
LTC4
Sphingosine-1-phosphate (CID: 5283560)
Mast cells
CysLT1–2
Leukotriene C4 (CID: 5280493)
Lipid mediators
BMMC
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Snippet Sphingosine-1-phosphate (S1P), platelet activating factor (PAF) and eicosanoids are bioactive lipid mediators abundantly produced by antigen-stimulated mast...
Sphingosine-1phosphate (S1P), platelet activating factor (PAF) and eicosanoids are bioactive lipid mediators abundantly produced by antigen-stimulated mast...
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SubjectTerms Allergy
Animals
Eicosanoids
Eicosanoids - metabolism
Humans
Hypersensitivity - immunology
Lipid mediators
Lysophospholipids - biosynthesis
Lysophospholipids - metabolism
Mast cells
Mast Cells - cytology
Mast Cells - metabolism
Mast Cells - pathology
Platelet activating factor
Platelet Activating Factor - metabolism
Sphingosine - analogs & derivatives
Sphingosine - biosynthesis
Sphingosine - metabolism
Sphingosine-1-phosphate
Title Sphingosine-1-phosphate and other lipid mediators generated by mast cells as critical players in allergy and mast cell function
URI https://dx.doi.org/10.1016/j.ejphar.2015.02.058
https://www.ncbi.nlm.nih.gov/pubmed/25941085
https://search.proquest.com/docview/1780511623
https://search.proquest.com/docview/1794494997
https://pubmed.ncbi.nlm.nih.gov/PMC4630215
Volume 778
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