Sakurai Daiju, Yamasaki Sho, Arase Kanako, Park Seung Yong, Arase Hisashi, Konno Akiyoshi, Saito Takashi
Departments of Molecular Genetics and Otorhinolaryngology, Graduate School of Medicine, Chiba University, Chiba, Japan.
J Immunol. 2004 Feb 15;172(4):2374-81. doi: 10.4049/jimmunol.172.4.2374.
The cross-linking of IgE-bound FcepsilonRI by Ags triggers mast cell activation leading to allergic reactions. The in vivo contribution of FcepsilonRIgamma signaling to IgE/FcepsilonRI-mediated mast cell responses has not yet been elucidated. In this study FcepsilonRIgamma(-/-) mast cells were reconstituted with either wild-type or mutant FcepsilonRIgamma in transgenic mice and transfected mast cells in vitro. We demonstrate that FcepsilonRIgamma-immunoreceptor tyrosine-based activation motif is essential for degranulation, cytokine production, and PG synthesis as well as for passive systemic anaphylaxis. Recent reports have suggested that cell surface FcepsilonRI expression and mast cell survival are regulated by IgE in the absence of Ag, although the molecular mechanism is largely unknown. We also found that the promotion of mast cell survival by IgE without Ags is mediated by signals through the FcepsilonRIgamma-immunoreceptor tyrosine-based activation motif. In contrast, the IgE-mediated up-regulation of FcepsilonRI is independent of FcepsilonRIgamma signaling. These results indicate that FcepsilonRIgamma-mediated signals differentially regulate the receptor expression, activation, and survival of mast cells and systemic anaphylaxis.
抗原使结合IgE的FcepsilonRI发生交联，触发肥大细胞活化，导致过敏反应。FcepsilonRIγ信号在体内对IgE/FcepsilonRI介导的肥大细胞反应的作用尚未阐明。在本研究中，在转基因小鼠中用野生型或突变型FcepsilonRIγ重建FcepsilonRIγ(-/-)肥大细胞，并在体外转染肥大细胞。我们证明，FcepsilonRIγ免疫受体酪氨酸基激活基序对于脱颗粒、细胞因子产生、PG合成以及被动全身过敏反应至关重要。最近的报告表明，在没有抗原的情况下，IgE可调节细胞表面FcepsilonRI的表达和肥大细胞存活，尽管其分子机制尚不清楚。我们还发现，无抗原时IgE对肥大细胞存活的促进作用是由通过FcepsilonRIγ免疫受体酪氨酸基激活基序的信号介导的。相反，IgE介导的FcepsilonRI上调与FcepsilonRIγ信号无关。这些结果表明，FcepsilonRIγ介导的信号差异调节肥大细胞的受体表达、活化和存活以及全身过敏反应。
