Kubo S, Matsuoka K, Taya C, Kitamura F, Takai T, Yonekawa H, Karasuyama H
Department of Laboratory Animal Science and Immunology, Tokyo Metropolitan Organization for Medical Science, Tokyo Metropolitan Institute of Medical Science, Tokyo, Japan.
J Immunol. 2001 Sep 15;167(6):3427-34. doi: 10.4049/jimmunol.167.6.3427.
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.
研究表明，免疫球蛋白E（IgE）与肥大细胞上的FcεRI结合会导致FcεRI表达增加，进而增强肥大细胞释放依赖IgE的化学介质。因此，预防IgE介导的FcεRI上调可能是治疗过敏性疾病的一种有前景的策略。然而，IgE介导的FcεRI上调机制尚未完全阐明。在本研究中，我们分析了腹膜肥大细胞和骨髓来源肥大细胞上FcεRI的动力学。在布雷菲德菌素A存在的情况下，布雷菲德菌素A可阻止新的FcεRI分子转运至细胞表面，肥大细胞上无IgE结合的FcεRI水平在培养过程中急剧下降，而有IgE结合的FcεRI水平则保持稳定。相比之下，即使在没有其配体的情况下，同一细胞上FcγRIII的水平也保持稳定，这表明无IgE结合的FcεRI的不稳定性是由FcεRIα链而非β链和γ链导致的。据我们分析，没有证据支持IgE与FcεRI结合促进FcεRI合成和/或转运至细胞表面这一观点。因此，通过IgE结合使FcεRI在细胞表面稳定和积累似乎是IgE介导的FcεRI上调的主要机制。
