Lung inflammation and epithelial changes in a murine model of atopic asthma
Lung inflammation and epithelial changes in a murine model of atopic asthma
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DOI：
10.1165/ajrcmb.14.5.8624247
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发表时间：
1996-05-01
影响因子：
6.4
通讯作者：
Fattah, D
中科院分区：
文献类型：
--
作者：
Blyth, DI;Pedrick, MS;Fattah, D
过敏原诱导的气道炎症和上皮细胞表型变化的小鼠模型，以及这些事件的时间进程，进行了描述。小鼠致敏卵清蛋白使用促炎剂的协议，并通过多次肠内滴注卵清蛋白的非手术技术的挑战。人类特应性哮喘的许多特征在小鼠中被观察到。过敏原激发后肺组织和气道出现明显的嗜酸性粒细胞浸润，其严重程度随着每次激发而增加，血液中嗜酸性粒细胞的数量也增加。淋巴细胞、中性粒细胞和单核细胞也侵入肺。气道巨噬细胞显示出活化的迹象，它们的外观类似于从抗原激发的人哮喘气道中回收的那些。气道上皮增厚，终末细支气管和大气道中显示明显的杯状细胞增生。反复激发后，气道上皮基底膜下的网状层显示纤维化，重现了人类哮喘常见的组织学特征。杯状细胞增生开始出现之前，嗜酸性粒细胞或淋巴细胞已迁移通过气道上皮，并持续至少11天后，第三次intrichelheal挑战与卵清蛋白，尽管在肺和气道的炎症细胞的数量已减少到接近正常水平的4天。粘液堵塞了一些呼吸道。这些结果表明，在气道上皮细胞的一些表型变化，在肺过敏反应，可以开始之前的嗜酸性粒细胞或淋巴细胞迁移通过上皮层。
A murine model of allergen-induced airway inflammation and epithelial phenotypic change, and the time-courses of these events, are described. Mice were sensitized to ovalbumin using an adjuvant-free protocol, and challenged by multiple intratracheal instillations of ovalbumin by a non-surgical technique. Many of the characteristic features of human atopic asthma were seen in the mice. A marked eosinophilic infiltration of lung tissue and airways followed allergen challenge, and its severity increased with each challenge, as did the number of eosinophils in the blood. Lymphocytes, neutrophils, and monocytes also invaded the lungs. Airway macrophages showed signs of activation, their appearance resembling those recovered from antigen-challenged human asthmatic airways. The airway epithelium was thickened and displayed a marked goblet cell hyperplasia in terminal bronchioles and larger airways. After repeated challenges, the reticular layer beneath the basement membrane of the airway epithelium showed fibrosis, reproducing a commonly observed histologic feature of human asthma. Goblet cell hyperplasia began to appear before eosinophils or lymphocytes had migrated across the airway epithelium, and persisted for at least 11 days after the third intratracheal challenge with ovalbumin, despite the number of inflammatory cells in the lungs and airways having decreased to near-normal levels by 4 days. Plugs of mucus occluded some of the airways. These results indicate that some of the phenotypic changes in airway epithelium that follow an allergic response in the lung can be initiated before the migration of eosinophils or lymphocytes across the epithelial layer.