An inhalation model of airway allergic response to inhalation of environmental Aspergillus fumigatus conidia in sensitized BALB/c mice
An inhalation model of airway allergic response to inhalation of environmental Aspergillus fumigatus conidia in sensitized BALB/c mice
复制标题
DOI：
10.3109/13693786.2010.485582
复制
发表时间：
2010-12-01
期刊：
影响因子：
2.9
通讯作者：
Schuh, Jane M.
中科院分区：
文献类型：
--
作者：
Hoselton, Scott A.;Samarasinghe, Amali E.;Schuh, Jane M.
接触真菌可能会引发人类的一些肺部疾病，包括过敏性哮喘。真菌致敏与哮喘的严重程度有关，尽管这种增加的病理基础仍然不明确。为了创造模拟人类环境中真菌过敏原暴露的条件，在先前对曲霉抗原提取物致敏的小鼠中，采用了只经鼻子吸入烟曲霉分生孢子的方法。给BALB/c小鼠皮下和腹腔注射明矾中的可溶性烟曲霉菌提取物，然后将相同的真菌抗原溶解在生理盐水中进行三次鼻腔接种，以诱导全局致敏，方式与其他已发表的模型相似。然后，这些动物被吸入10分钟的活孢子，这些孢子直接从成熟的烟曲霉菌培养物表面吹出。吸入烟曲霉孢子一次后，变态反应性肺部炎症和气道高反应性显著高于幼稚动物和对烟曲霉菌抗原致敏但未用分生孢子攻击的动物。吸入分生孢子改变了肺的结构，与对照组相比，肺上皮厚度显著增加，杯状细胞化生和支气管周围胶原沉积显著增加。此外，组织切片的α-平滑肌肌动蛋白染色显示真菌攻击后支气管周围平滑肌质量增加的视觉证据。总之，通过提供更自然的暴露途径，将活的烟曲霉分生孢子输送到BALB/c小鼠的致敏呼吸道，通过提供更自然的暴露途径，促进了肺部对真菌的反应的研究，并首次证明了在小鼠模型中暴露于吸入真菌分生孢子时，纤维化和平滑肌变化的持续发展。
Fungal exposure may elicit a number of pulmonary diseases in man, including allergic asthma. Fungal sensitization is linked to asthma severity, although the basis for this increased pathology remains ambiguous. To create conditions simulating environmental fungal allergen exposure in a human, nose-only inhalation delivery of Aspergillus fumigatus conidia was employed in mice previously sensitized to Aspergillus antigen extract. BALB/c mice were immunized with subcutaneous and intraperitoneal injections of soluble A. fumigatus extract in alum, which was followed by three intranasal inoculations of the same fungal antigens dissolved in saline to elicit global sensitization in a manner similar to other published models. The animals were then challenged with a 10-min inhaled dose of live conidia blown directly from the surface of a mature A. fumigatus culture. After a single challenge with inhaled A. fumigatus conidia, allergic pulmonary inflammation and airway hyperresponsiveness were significantly increased above that of either naive animals or animals that had been sensitized to A. fumigatus antigens but not challenged with conidia. The architecture of the lung was changed by inhalation of conidia when compared to controls in that there were significant increases in epithelial thickness, goblet cell metaplasia, and peribronchial collagen deposition. Additionally, alpha-smooth muscle actin staining of histological sections showed visual evidence of increased peribronchial smooth muscle mass after fungal challenge. In summary, the delivery of live A. fumigatus conidia to the sensitized airways of BALB/c mice advances the study of the pulmonary response to fungi by providing a more natural route of exposure and, for the first time, demonstrates the consistent development of fibrosis and smooth muscle changes accompanying exposure to inhaled fungal conidia in a mouse model.