Mast cell maturation is driven via a group III phospholipase A2-prostaglandin D2-DP1 receptor paracrine axis

Nat Immunol. 2013 Jun;14(6):554-63. doi: 10.1038/ni.2586. Epub 2013 Apr 28.

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

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Blotting, Western
  • Bone Marrow Cells / immunology
  • Bone Marrow Cells / metabolism
  • Cell Differentiation / genetics
  • Cell Differentiation / immunology
  • Cells, Cultured
  • Fibroblasts / cytology
  • Fibroblasts / immunology
  • Fibroblasts / metabolism
  • Gene Expression Profiling
  • Group III Phospholipases A2 / genetics
  • Group III Phospholipases A2 / immunology*
  • Group III Phospholipases A2 / metabolism
  • Humans
  • Intramolecular Oxidoreductases / genetics
  • Intramolecular Oxidoreductases / immunology
  • Intramolecular Oxidoreductases / metabolism
  • Lipocalins / genetics
  • Lipocalins / immunology
  • Lipocalins / metabolism
  • Mast Cells / immunology*
  • Mast Cells / metabolism
  • Mast Cells / ultrastructure
  • Mice
  • Mice, 129 Strain
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Microscopy, Electron, Transmission
  • Oligonucleotide Array Sequence Analysis
  • Paracrine Communication / genetics
  • Paracrine Communication / immunology*
  • Prostaglandin D2 / immunology*
  • Prostaglandin D2 / metabolism
  • Receptors, Prostaglandin / genetics
  • Receptors, Prostaglandin / immunology*
  • Receptors, Prostaglandin / metabolism
  • Reverse Transcriptase Polymerase Chain Reaction

Substances

  • Lipocalins
  • Receptors, Prostaglandin
  • prostanoid D receptor 1, mouse
  • Group III Phospholipases A2
  • PLA2G3 protein, mouse
  • Intramolecular Oxidoreductases
  • prostaglandin R2 D-isomerase
  • Prostaglandin D2

Associated data

  • GEO/GSE44980