Airway hyperresponsiveness and airway obstruction in transgenic mice morphologic correlates in mice overexpressing interleukin (IL)-11 and IL-6 in the lung
Airway hyperresponsiveness and airway obstruction in transgenic mice morphologic correlates in mice overexpressing interleukin (IL)-11 and IL-6 in the lung
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DOI：
10.1165/ajrcmb.22.3.3690
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发表时间：
2000-03-01
影响因子：
6.4
通讯作者：
Elias, JA
中科院分区：
文献类型：
--
作者：
Kuhn, C;Homer, RJ;Elias, JA
了解气道反应性和气流变化的来源对于阐明哮喘、阻塞性肺病和其他肺部疾病的病理生理学是很重要的。两个密切相关的细胞因子在小鼠肺中的转基因表达对这些参数产生相反的影响。白细胞介素（IL）-6没有改变基础气道阻力和乙酰甲胆碱反应性降低，而IL-11引起气道阻塞和增加气道反应乙酰甲胆碱。为了阐明这些差异，我们检查了组织切片，并使用形态测定法比较1至2月龄表达IL-6或IL-11的转基因小鼠和同窝对照小鼠的细支气管和实质尺寸。两种转基因株表现出相似的肺气肿样的空气空间扩大，结节状的单核细胞聚集，气道壁增厚，上皮下气道纤维化。与同窝对照小鼠相比，IL-6小鼠的细支气管口径增加约50%，气道壁厚度增加，与气道大小增加成比例。相比之下，IL-11转基因小鼠的重塑反应更强烈。在外径和管腔直径正常的气道中也可见，因此与其气道口径不成比例。这些结果支持这样的假设，即呼吸道的结构改变和由此产生的口径变化可以对气道生理和反应性产生重要影响。
Understanding the sources of variation in airway reactivity and airflow is important for unraveling the pathophysiology of asthma, obstructive lung disease, and other pulmonary disorders. Transgenic expression of two closely related cytokines in the mouse lung produced opposite effects on these parameters. Interleukin (IL)-6 did not alter basal airways resistance and decreased methacholine responsiveness, whereas IL-11 caused airways obstruction and increased airway responses to methacholine. To clarify these differences we examined histologic sections and used morphometry to compare bronchiolar and parenchymal dimensions in 1- to 2-mo-old transgenic mice expressing IL-6 or IL-11 and littermate control mice. Both transgenic strains showed similar emphysema-like airspace enlargement, nodular peribronchiolar collections of mononuclear cells, thickening of airway walls, and subepithelial airway fibrosis. When compared with littermate control mice, the IL-6 mice showed an approximately 50% increase in the caliber of their bronchioles and an increase in airway wall thickness that was in proportion to the increase in the size of their airways. In contrast, the remodeling response was more robust in the IL-11 transgenic mice. It was also seen in airways with normal external and luminal diameters and thus was out of proportion to the caliber of their airways. These results support the hypothesis that structural alterations and resulting caliber changes of respiratory airways can have important effects on airway physiology and reactivity.