Mayr S I, Zuberi R I, Liu F-T
La Jolla Institute for Allergy and Immunology, La Jolla, CA 95817, USA.
Braz J Med Biol Res. 2003 Jul;36(7):821-7. doi: 10.1590/s0100-879x2003000700001. Epub 2003 Jun 26.
Immunoglobulin E (IgE) and mast cells are believed to play important roles in allergic inflammation. However, their contributions to the pathogenesis of human asthma have not been clearly established. Significant progress has been made recently in our understanding of airway inflammation and airway hyperresponsiveness through studies of murine models of asthma and genetically engineered mice. Some of the studies have provided significant insights into the role of IgE and mast cells in the allergic airway response. In these models mice are immunized systemically with soluble protein antigens and then receive an antigen challenge through the airways. Bronchoalveolar lavage fluid from mice with allergic airway inflammation contains significant amounts of IgE. The IgE can capture the antigen presented to the airways and the immune complexes so formed can augment allergic airway response in a high-affinity IgE receptor (FcepsilonRI)-dependent manner. Previously, there were conflicting reports regarding the role of mast cells in murine models of asthma, based on studies of mast cell-deficient mice. More recent studies have suggested that the extent to which mast cells contribute to murine models of asthma depends on the experimental conditions employed to generate the airway response. This conclusion was further supported by studies using FcepsilonRI-deficient mice. Therefore, IgE-dependent activation of mast cells plays an important role in the development of allergic airway inflammation and airway hyperresponsiveness in mice under specific conditions. The murine models used should be of value for testing inhibitors of IgE or mast cells for the development of therapeutic agents for human asthma.
免疫球蛋白E（IgE）和肥大细胞被认为在过敏性炎症中起重要作用。然而，它们对人类哮喘发病机制的贡献尚未明确确立。最近，通过对哮喘小鼠模型和基因工程小鼠的研究，我们在理解气道炎症和气道高反应性方面取得了重大进展。其中一些研究为IgE和肥大细胞在过敏性气道反应中的作用提供了重要见解。在这些模型中，小鼠用可溶性蛋白抗原进行全身免疫，然后通过气道接受抗原攻击。患有过敏性气道炎症的小鼠的支气管肺泡灌洗液中含有大量IgE。IgE可以捕获呈递给气道的抗原，如此形成的免疫复合物可以以高亲和力IgE受体（FcepsilonRI）依赖性方式增强过敏性气道反应。以前，基于对肥大细胞缺陷小鼠的研究，关于肥大细胞在哮喘小鼠模型中的作用存在相互矛盾的报道。最近的研究表明，肥大细胞对哮喘小鼠模型的贡献程度取决于用于产生气道反应的实验条件。使用FcepsilonRI缺陷小鼠的研究进一步支持了这一结论。因此，在特定条件下，IgE依赖性肥大细胞活化在小鼠过敏性气道炎症和气道高反应性的发展中起重要作用。所使用的小鼠模型对于测试IgE或肥大细胞抑制剂以开发治疗人类哮喘的药物应该具有价值。
