Drastic up-regulation of Fcepsilonri on mast cells is induced by IgE binding through stabilization and accumulation of Fcepsilonri on the cell surface

J Immunol. 2001 Sep 15;167(6):3427-34. doi: 10.4049/jimmunol.167.6.3427.

Abstract

It has been shown that IgE binding to FcepsilonRI on mast cells results in increased FcepsilonRI expression, which in turn enhances IgE-dependent chemical mediator release from mast cells. Therefore, prevention of the IgE-mediated FcepsilonRI up-regulation would be a promising strategy for management of allergic disorders. However, the mechanism of IgE-mediated FcepsilonRI up-regulation has not been fully elucidated. In this study, we analyzed kinetics of FcepsilonRI on peritoneal mast cells and bone marrow-derived mast cells. In the presence of brefeldin A, which prevented transport of new FcepsilonRI molecules to the cell surface, levels of IgE-free FcepsilonRI on mast cells decreased drastically during culture, whereas those of IgE-bound FcepsilonRI were stable. In contrast, levels of FcgammaRIII on the same cells were stable even in the absence of its ligand, indicating that FcepsilonRI alpha-chain, but not beta- and gamma-chains, was responsible for the instability of IgE-free FcepsilonRI. As far as we analyzed, there was no evidence to support the idea that IgE binding to FcepsilonRI facilitated synthesis and/or transport of FcepsilonRI to the cell surface. Therefore, the stabilization and accumulation of FcepsilonRI on the cell surface through IgE binding appears to be the major mechanism of IgE-mediated FcepsilonRI up-regulation.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bone Marrow Cells / drug effects
  • Bone Marrow Cells / metabolism
  • Brefeldin A / pharmacology
  • Cell Membrane / metabolism*
  • Drug Stability
  • Humans
  • Immunoglobulin E / blood
  • Immunoglobulin E / immunology
  • Immunoglobulin E / metabolism
  • Immunoglobulin E / pharmacology*
  • Ligands
  • Mast Cells / drug effects*
  • Mast Cells / metabolism
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Protein Binding
  • Protein Subunits
  • Receptors, IgE / biosynthesis*
  • Receptors, IgE / chemistry
  • Receptors, IgE / genetics
  • Recombinant Fusion Proteins / pharmacology
  • Transcription, Genetic
  • Up-Regulation / drug effects*

Substances

  • Ligands
  • Protein Subunits
  • Receptors, IgE
  • Recombinant Fusion Proteins
  • Brefeldin A
  • Immunoglobulin E