免疫球蛋白E信号受体与气喘.doc

Immunoglobulin E ReceptorSignaling and Asthma* First Published on July 28, 2011, doi: 10.1074/jbc.R110.205104 September 23, 2011 The Journal of Biological Chemistry, 286, 32891-32897. Lawren C. Wu1 From the Department of Immunology, Genentech, Incorporated,South San Francisco, California 94080 Elevated IgE levels and increased IgE sensitization to allergensare central features of allergic asthma. IgE binds to the high-affinity Fc_ receptor I(Fc_RI) on mast cells, basophils, anddendritic cells and mediates the activation of these cells uponantigen-induced cross-linking of IgE-bound Fc_RI. Fc_RI activation proceeds through a network of signaling molecules andadaptor proteins and is negatively regulated by a number of cell surface and intracellular proteins. Therapeutic neutralization of serum IgE in moderate-to-severe allergic asthmatics reduces the frequency of asthma exacerbations through a reduction in cell surface Fc_RI expression that results in decreased Fc_RI activation,leading to improved asthma control. Our increasing understanding of IgE receptor signaling may lead to the development of novel therapeutics for the treatment of asthma. 免疫球蛋白E信号受体与气喘 由过敏原引起的IgE的含量升高及敏感度增强是气喘的主要特征。IgE对肥大细胞、嗜碱性粒细胞和树突细胞的Fc受体I具有较高的亲和力，通过与Fc受体I交叉结合来调节这些细胞相应抗原的活性。信号分子与适配器蛋白相互作用激活Fc受体I的过程是多种细胞表面蛋白和细胞内蛋白的负调控作用。对患有不同程度的过敏气喘者采用血清IgE化学中和疗法，能够降低患者的气喘频率，其作用机理是抑制细胞表面Fc受体I的表达以降低其活性，使气喘得以控制。随着我们对IgE受体的深入理解或许能够研究出治疗气喘的新疗法。 Summary A substantial network of signaling molecules and adaptor proteins that function downstream of Fc_RI activation has beendefined.Future studies will continue to elucidate the cell and membrane biology of Fc_RI signaling, novel cell surface and intracellular mediators of Fc_RI activation, mechanisms of intracellular calcium signaling, and new inhibitory proteins that negatively regulate parts of the signaling network downstream of Fc_RI activation. Our increasing understanding of Fc_RI signaling may lead to the development of new the rapeutics that inhibit Fc_RI activat