title: Drastic up-regulation of Fcepsilonri on mast cells is induced by IgE binding through stabilization and accumulation of Fcepsilonri on the cell surface.
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.
authors.affiliation: Department of Laboratory Animal Science and Immunology, Tokyo Metropolitan Organization for Medical Science, Tokyo Metropolitan Institute of Medical Science, Tokyo, Japan. skubo@rinshoken.or.jp
authors.forename: S
authors.initials: S
authors.lastname: Kubo
authors.forename: K
authors.initials: K
authors.lastname: Matsuoka
authors.forename: C
authors.initials: C
authors.lastname: Taya
authors.forename: F
authors.initials: F
authors.lastname: Kitamura
authors.forename: T
authors.initials: T
authors.lastname: Takai
authors.forename: H
authors.initials: H
authors.lastname: Yonekawa
authors.forename: H
authors.initials: H
authors.lastname: Karasuyama
mesh_terms: D000818:Animals; D001854:Bone Marrow Cells / Q000187:drug effects / Q000378:metabolism; D020126:Brefeldin A / Q000494:pharmacology; D002462:Cell Membrane / Q000378:metabolism*; D004355:Drug Stability; D006801:Humans; D007073:Immunoglobulin E / Q000097:blood / Q000276:immunology / Q000378:metabolism / Q000494:pharmacology*; D008024:Ligands; D008407:Mast Cells / Q000187:drug effects* / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D011485:Protein Binding; D021122:Protein Subunits; D017455:Receptors, IgE / Q000096:biosynthesis* / Q000737:chemistry / Q000235:genetics; D011993:Recombinant Fusion Proteins / Q000494:pharmacology; D014158:Transcription, Genetic; D015854:Up-Regulation / Q000187:drug effects*
chemical_list: D008024:Ligands; D021122:Protein Subunits; D017455:Receptors, IgE; D011993:Recombinant Fusion Proteins; D020126:Brefeldin A; D007073:Immunoglobulin E