Excessive inflammatory response of cystic fibrosis mice to bronchopulmonary infection with Pseudomonas aeruginosa
Excessive inflammatory response of cystic fibrosis mice to bronchopulmonary infection with Pseudomonas aeruginosa
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DOI：
10.1172/jci119828
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发表时间：
1997-12-01
影响因子：
15.9
通讯作者：
Ferkol, T
中科院分区：
文献类型：
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作者：
van Heeckeren, A;Walenga, R;Ferkol, T
在囊性纤维化（CF）中，气道上皮细胞和粘膜下腺中囊性纤维化跨膜传导调节因子（CFTR）功能缺陷导致铜绿假单胞菌慢性肺部感染。肺部感染会引起宿主强烈的炎症反应，导致进行性化脓性肺病，但CF小鼠模型不能自发发展为肺部疾病。我们利用慢性假单胞菌支气管内感染动物模型，研究了支气管肺感染对CFTR基因S489X突变纯合小鼠的影响。将无菌琼脂糖球或含有黏液样铜绿假单胞菌的球液灌注于正常小鼠或CF小鼠的右肺，接种含假单胞菌球的CF小鼠死亡率明显高于正常小鼠；感染CF小鼠在感染后10 d内死亡的比例为82%，而正常小鼠仅为23% （P = 0.023）。感染后3 d和死亡前，CF小鼠支气管肺泡灌洗液中炎症介质tnf - α、小鼠巨噬细胞炎症蛋白-2和KC/N51的浓度明显高于正常小鼠，这种炎症反应也与接种后CF和正常窝鼠体重下降有关。该模型可以检查CF中细菌感染、炎症、细胞和遗传缺陷之间的关系。
In cystic fibrosis (CF), defective function of the cystic fibrosis transmembrane conductance regulator (CFTR) in airway epithelial cells and submucosal glands results in chronic pulmonary infection with Pseudomonas aeruginosa. The pulmonary infection incites an intense host inflammatory response, causing progressive suppurative pulmonary disease, Mouse models of CF, however, fail to develop pulmonary disease spontaneously, We examined the effects of bronchopulmonary infection on mice homozygous for the S489X mutation of the CFTR gene using an animal model of chronic Pseudomonas endobronchial infection, Slurries of sterile agarose beads or beads containing a clinical isolate of mucoid P. aeruginosa were instilled in the right lung of normal or CF mice, The mortality of CF mice inoculated with Pseudomonas-laden beads was significantly higher than that of normal animals: 82% of infected CF mice, but only 23% of normal mice, died within 10 d of infection (P = 0.023), The concentration of inflammatory mediators, including TNF-alpha, murine macrophage inflammatory protein-2, and KC/N51, in bronchoalveolar lavage fluid in CF mice 3 d after infection and before any mortality, was markedly elevated compared with normal mice, This inflammatory response also correlated with weight loss observed in both CF and normal littermates after inoculation, Thus, this model may permit, examination of the relationship of bacterial infections, inflammation, and the cellular and genetic defects in CF.