Abstract
Microenvironment-based alterations in phenotypes of mast cells influence the susceptibility to anaphylaxis, yet the mechanisms underlying proper maturation of mast cells toward an anaphylaxis-sensitive phenotype are incompletely understood. Here we report that PLA2G3, a mammalian homolog of anaphylactic bee venom phospholipase A2, regulates this process. PLA2G3 secreted from mast cells is coupled with fibroblastic lipocalin-type PGD2 synthase (L-PGDS) to provide PGD2, which facilitates mast-cell maturation via PGD2 receptor DP1. Mice lacking PLA2G3, L-PGDS or DP1, mast cell-deficient mice reconstituted with PLA2G3-null or DP1-null mast cells, or mast cells cultured with L-PGDS-ablated fibroblasts exhibited impaired maturation and anaphylaxis of mast cells. Thus, we describe a lipid-driven PLA2G3-L-PGDS-DP1 loop that drives mast cell maturation.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Blotting, Western
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Bone Marrow Cells / immunology
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Bone Marrow Cells / metabolism
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Cell Differentiation / genetics
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Cell Differentiation / immunology
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Cells, Cultured
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Fibroblasts / cytology
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Fibroblasts / immunology
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Fibroblasts / metabolism
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Gene Expression Profiling
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Group III Phospholipases A2 / genetics
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Group III Phospholipases A2 / immunology*
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Group III Phospholipases A2 / metabolism
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Humans
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Intramolecular Oxidoreductases / genetics
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Intramolecular Oxidoreductases / immunology
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Intramolecular Oxidoreductases / metabolism
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Lipocalins / genetics
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Lipocalins / immunology
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Lipocalins / metabolism
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Mast Cells / immunology*
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Mast Cells / metabolism
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Mast Cells / ultrastructure
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Mice
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Mice, 129 Strain
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Mice, Inbred C57BL
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Mice, Knockout
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Microscopy, Electron, Transmission
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Oligonucleotide Array Sequence Analysis
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Paracrine Communication / genetics
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Paracrine Communication / immunology*
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Prostaglandin D2 / immunology*
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Prostaglandin D2 / metabolism
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Receptors, Prostaglandin / genetics
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Receptors, Prostaglandin / immunology*
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Receptors, Prostaglandin / metabolism
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Reverse Transcriptase Polymerase Chain Reaction
Substances
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Lipocalins
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Receptors, Prostaglandin
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prostanoid D receptor 1, mouse
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Group III Phospholipases A2
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PLA2G3 protein, mouse
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Intramolecular Oxidoreductases
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prostaglandin R2 D-isomerase
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Prostaglandin D2