Phenotypic and physiologic characterization of transgenic mice expressing interleukin 4 in the lung: Lymphocytic and eosinophilic inflammation without airway hyperreactivity
Phenotypic and physiologic characterization of transgenic mice expressing interleukin 4 in the lung: Lymphocytic and eosinophilic inflammation without airway hyperreactivity
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DOI：
10.1073/pnas.93.15.7821
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发表时间：
1996-07-23
影响因子：
11.1
通讯作者：
Flavell, RA
中科院分区：
文献类型：
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作者：
Rankin, JA;Picarella, DE;Flavell, RA
为了研究白细胞介素4(IL-4)在体内气道炎症中的作用，并直接探讨其与气道反应性的关系，我们建立了由大鼠Clara细胞10蛋白启动子调控小鼠IL-4基因的转基因小鼠。仅在肺中检测到表达，在胸腺、心脏、肝脏、脾、肾或子宫中未检测到表达。IL-4的表达可引起气管、支气管和细支气管上皮细胞肥大。肥大至少部分是由于粘液糖蛋白的积聚。实质组织学检查显示多核巨噬细胞，偶见细胞孤岛，主要由嗜酸性粒细胞或淋巴细胞组成。肺灌洗液分析显示有白细胞渗入，由淋巴细胞、中性粒细胞和嗜酸性粒细胞组成。表达IL-4的小鼠有更大的基础气道阻力，但对乙酰甲胆碱没有表现出高反应性。因此，IL-4在肺内的选择性表达引起以上皮细胞肥大为特征的炎症反应，并聚集巨噬细胞、淋巴细胞、嗜酸性粒细胞和中性粒细胞，而不会改变吸入乙酰甲胆碱后的呼吸道反应性。
To investigate the contribution of interleukin-4 (IL-4) to airway inflammation in vivo and to explore directly its relationship to airway reactivity, we created transgenic mice in which the murine cDNA for IL-4 was regulated by the rat Clara cell 10 protein promoter. Expression was detected only in the lung and not in thymus, heart, liver, spleen, kidney, or uterus. The expression of IL-4 elicited hypertrophy of epithelial cells of the trachea, bronchi, and bronchioles. Hypertrophy is due, at least in part, to the accumulation of mucus glycoprotein. Histologic examination of parenchyma revealed multinucleated macrophages and occasional islands of cells consisting largely of eosinophils or lymphocytes. Analysis of lung lavage fluid revealed the presence of a leukocytic infiltrate consisting of lymphocytes, neutrophils and eosinophils. Mice expressing IL-4 had greater baseline airway resistance but did not demonstrate hyperreactivity to methacholine. Thus, the expression of IL-4 selectively within the lung elicits an inflammatory response characterized by epithelial cell hypertrophy, and the accumulation of macrophages, lymphocytes, eosinophils, and neutrophils without resulting in an alteration in airway reactivity to inhaled methacholine.