A murine model of allergic rhinitis: Studies on the role of IgE in pathogenesis and analysis of the eosinophil influx elicited by allergen and eotaxin
A murine model of allergic rhinitis: Studies on the role of IgE in pathogenesis and analysis of the eosinophil influx elicited by allergen and eotaxin
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DOI：
10.1016/s0091-6749(98)70056-9
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发表时间：
1998-07-01
影响因子：
14.2
通讯作者：
Oettgen, HC
中科院分区：
文献类型：
--
作者：
van de Rijn, M;Mehlhop, PD;Oettgen, HC
背景：变应性鼻炎是一种发病率很高的常见病，其在人体中的病理生理研究一直很有限。鼻腔活检标本难以获得，鼻腔分泌物不完全反映粘膜的细胞和分子事件，ige介导的肥大细胞活化以及促进嗜酸性粒细胞发育和趋化的因子的阐述可能参与了发病机制。目的：建立小鼠变应性鼻炎模型，探讨IgE在变应性鼻炎发病机制中的作用，并研究IL-5和eotasin在鼻黏膜中的作用。方法：采用烟曲霉（Aspergillus fumigatus, Af）蛋白提取物灌胃小鼠。在野生型和IgE缺陷（IgE(-/-)）动物中检测组织学变化。在野生型和IL-5转基因小鼠中评价了eotasin给药的效果。结果：af治疗小鼠的鼻黏膜嗜酸性粒细胞内流与人类相似，这种组织学与af诱导哮喘小鼠模型中观察到的不同，病理出现的时间过程与人类受试者相似。与野生型小鼠相比，rif处理的IgE（-/-）小鼠粘膜炎症浸润强度无差异。结论：我们描述了一种具有与人类疾病相似的嗜酸性粒细胞浸润的变应性鼻炎小鼠模型，并且已经证明鼻炎可以在缺乏IgE的情况下发生，我们已经证明在存在IL-5的情况下Eotaxin可以诱导嗜酸性粒细胞流入。
Background: Allergic rhinitis is a prevalent disease with significant morbidity, Studies of its pathophysiology in human subjects have been limited. Nasal biopsy specimens are difficult to obtain, and nasal secretions incompletely reflect the cellular and molecular events in the mucosa, IgE-mediated mast cell activation and the elaboration of factors promoting eosinophil development and chemotaxis are likely to participate in pathogenesis.Objectives: We sought to develop a murine model of allergic rhinitis, to use it to assess the role of IgE in pathogenesis, and to study the effects of IL-5 and eotasin in the nasal mucosa,Methods: A protein extract of Aspergillus fumigatus (Af) was instilled intranasally in mice. Histologic changes were examined in wild-type and IgE-deficient (IgE(-/-)) animals. The effect of eotasin administration was assessed in wild-type and IL-5 transgenic mice.Results: Af-treated mice developed a nasal mucosal eosinophil influx comparable to that described for humans, This histology was distinct from that observed in a murine model Af-induced asthma, The pathology appeared over a time course similar to that reported for human subjects. There was no difference in the intensity of the mucosal inflammatory infiltrate of rif-treated IgE(-/-) mice compared with wild-type mice. Eotaxin mas able to recruit eosinophils to the mucosa but only in IL-5 transgenic animals, Conclusion: We describe a murine model for allergic rhinitis with an eosinophilic infiltrate comparable to that found in human disease and have demonstrated that rhinitis can arise in the absence of IgE, We have shown that the eosinophil influx can be induced by eotaxin in the presence of IL-5.