Allergen-induced bronchial hyperreactivity and eosinophilic inflammation occur in the absence of IgE in a mouse model of asthma
Allergen-induced bronchial hyperreactivity and eosinophilic inflammation occur in the absence of IgE in a mouse model of asthma
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DOI：
10.1073/pnas.94.4.1344
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发表时间：
1997-02-18
影响因子：
11.1
通讯作者：
Oettgen, HC
中科院分区：
文献类型：
--
作者：
Mehlhop, PD;vandeRijn, M;Oettgen, HC
在哮喘患者中，IgE的升高与气道的过敏性炎症和支气管高反应性（BHR）两者相关。使用该疾病的小鼠模型的几项研究已经表明IgE在嗜酸性粒细胞性炎症的发病机制中以及在BHR的阻塞性气道生理学中起中心作用。一些哮喘的诊断研究和治疗策略是基于IgE在哮喘发病机制中的假定作用。在这里，我们使用的小鼠与一个无效突变的C β基因座表明，支气管炎症和BHR在过敏原吸入的反应都可以发生在IgE的情况下，我们证明，嗜酸性支气管炎症引起的小鼠模型过敏烟曲霉菌（Af）是伴随着哮喘的生理BHR。用Af提取物鼻内致敏野生型和IgE缺陷型小鼠，两组动物均出现支气管肺泡灌洗液嗜酸性粒细胞增多症和肺实质嗜酸性粒细胞增多症，这仅在野生型动物中伴有血清总IgE和Af特异性IgE水平升高，这种Af致敏方案在野生型小鼠和IgE缺陷型小鼠中均导致显著的BHR。与未致敏的野生型对照组相比，未致敏的IgE缺陷型小鼠的支气管反应性增加。我们得出结论，BHR和气道炎症可以通过IgE非依赖性机制完全表达。这些可能涉及由IgE以外的因子激活肥大细胞以及粘膜淋巴细胞介导的对过敏原的免疫应答。
In patients with asthma, elevations of IgE correlate both with allergic inflammation of the airways and with bronchial hyperreactivity (BHR), Several investigations, using mouse models of this disease, have indicated a central role for IgE in the pathogenesis of the eosinophilic inflammation as well as in the obstructive airway physiology of BHR. Some diagnostic studies and therapeutic strategies for asthma are based on the putative role of IgE in asthma pathogenesis. Here, we use mice with a null mutation of the C epsilon locus to show that bronchial inflammation and BHR in response to allergen inhalation both can occur in the absence of IgE, We demonstrate that the eosinophilic bronchial inflammation elicited in an established mouse model of hypersensitivity to Aspergillus fumigatus (Af) is accompanied by the asthmatic physiology of BHR. Wild-type and IgE-deficient mice were sensitized intranasally with Af extract, Both groups of animals developed bronchoalveolar lavage eosinophilia and pulmonary parenchymal eosinophilia, This was accompanied by increased serum Levels of total and Af-specific IgE in the wild-type animals only, This Af-sensitization protocol resulted in significant BHR in both wild-type mice and IgE-deficient mice, Interestingly, unsensitized IgE-deficient mice had increased bronchial responsiveness compared with unsensitized wildtype controls, We conclude that BHR and airways inflammation can be fully expressed via IgE-independent mechanisms. These may involve the activation of mast cells by factors other than IgE as well as a mucosal lymphocyte-mediated immune response to allergen.