PGD2 deficiency exacerbates food antigen-induced mast cell hyperplasia

Nat Commun. 2015 Jul 10;6:7514. doi: 10.1038/ncomms8514.

Abstract

Prostaglandin D2 (PGD2) is a major prostanoid secreted mainly by mast cells. Although PGD2 has been identified as a modulator of allergic inflammation, its precise role remains unclear. Here we investigate the role of PGD2 in food allergy. Oral administration of ovalbumin induces allergic responses in sensitized wild-type (WT) mice. Systemic gene deficiency of haematopoietic PGD synthase (H-PGDS(-/-)) exacerbates all of the manifestations accompanying severe mast cell hyperplasia in the intestine. Morphological studies show that c-kit/FcɛRI-positive WT mast cells strongly express H-PGDS. Transplantation of H-PGDS(-/-) mast cells also aggravates ovalbumin-induced mast cell hyperplasia and allergic symptoms in mast cell null mice. H-PGDS deficiency accelerates the production of SDF-1α and the activity of MMP-9 in the antigen-stimulated intestine. SDF-1α receptor blockade or MMP-9 inhibition relieves the exacerbated mast cell hyperplasia and manifestations observed in H-PGDS(-/-). Thus, PGD2 deficiency results in food antigen-induced mast cell hyperplasia.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adjuvants, Immunologic
  • Alum Compounds
  • Animals
  • Chemokine CXCL12 / immunology
  • Colon / immunology*
  • Colon / pathology
  • Cytokines / immunology
  • Enzyme-Linked Immunosorbent Assay
  • Food Hypersensitivity / immunology*
  • Hyperplasia
  • Intestines / immunology
  • Intestines / pathology
  • Intramolecular Oxidoreductases / genetics*
  • Lipocalins / genetics*
  • Mast Cells / immunology*
  • Mast Cells / pathology
  • Matrix Metalloproteinase 9 / immunology
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Microscopy, Electron
  • Ovalbumin
  • Prostaglandin D2 / deficiency
  • Prostaglandin D2 / immunology*
  • Reverse Transcriptase Polymerase Chain Reaction

Substances

  • Adjuvants, Immunologic
  • Alum Compounds
  • Chemokine CXCL12
  • Cxcl12 protein, mouse
  • Cytokines
  • Lipocalins
  • aluminum sulfate
  • Ovalbumin
  • Matrix Metalloproteinase 9
  • Mmp9 protein, mouse
  • Intramolecular Oxidoreductases
  • prostaglandin R2 D-isomerase
  • Prostaglandin D2