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

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.