Response to acute lung infection with mucoid Pseudomonas aeruginosa in cystic fibrosis mice
Response to acute lung infection with mucoid Pseudomonas aeruginosa in cystic fibrosis mice
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DOI：
10.1164/rccm.200506-917oc
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发表时间：
2006-02-01
影响因子：
24.7
通讯作者：
Davis, PB
中科院分区：
文献类型：
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作者：
van Heeckeren, AM;Schluchter, MD;Davis, PB
理由：囊性纤维化是由囊性纤维化跨膜传导调节基因缺陷引起的，该基因编码氯离子通道，但该氯离子通道在铜绿假单胞菌肺部感染引起的炎症中的作用仍有待明确。目的：我们验证了一种假设，即仅氯离子通道的丢失就足以引起对炎症刺激的过度炎症反应。我们研究了囊性纤维化小鼠和野生型小鼠对灌胃粘膜铜绿假单胞菌的反应。测量：测量宿主反应包括存活、体重变化、肺形态测量、细菌清除率和炎症介质，并评估支气管肺泡灌洗液中的细胞计数。主要结果：与野生型小鼠相比，根据给药剂量和给药频率的不同，囊性纤维化小鼠的死亡率、体重减轻程度、肺病理评分、炎症介质和中性粒细胞水平明显更高，即使在细菌被清除后也是如此。令人惊讶的是，囊性纤维化小鼠体内的细菌被清除的速度和野生型小鼠一样快，而且没有观察到败血症。粘液样铜绿假单胞菌在囊性纤维化小鼠和野生型小鼠中均不能建立慢性肺部感染。结论：与野生型对照相比，面对黏液性铜绿假单胞菌肺部感染时，缺乏这种氯离子通道足以引起夸大的炎症和更高的死亡率。要确定慢性感染，可能需要其他因素，如细菌捕获或清除不良。
Rationale: Cystic fibrosis is caused by defects in the cystic fibrosis transmembrane conductance regulator gene, which codes for a chloride channel, but the role of this chloride channel in inflammation induced by lung infection with Pseudomonas aeruginosa remains to be defined.Objectives: We tested the hypothesis that loss of this chloride channel alone is sufficient to cause excessive inflammation in response to inflammatory stimuli.Methods. We investigated the response of cystic fibrosis and wildtype mice to mucoid P. aeruginosa administered by insufflation.Measurements: The host responses measured included survival, weight change, lung morphometry, bacterial clearance, and inflammatory mediators, and cell counts were assessed in bronchoalveolar lavage fluid.Main Results: Depending on the dose administered and frequency of dosing, cystic fibrosis mice experienced significantly higher mortality rates, greater weight loss, higher lung pathology scores, and higher inflammatory mediator and neutrophil levels compared with wild-type mice, even after the bacteria had been cleared. Surprisingly, bacteria were cleared just as rapidly in cystic fibrosis mice as in wild-type mice, and sepsis was not observed. Chronic lung infections could not be established with mucoid P. aeruginosa in either cystic fibrosis or wild-type mice.Conclusions: Absence of this chloride channel alone appears sufficient for exaggerated inflammation and excess mortality compared with wild-type controls in the face of mucoid P. aeruginosa lung infection. To establish chronic infection, additional factors such as bacterial trapping or poor clearance may be required.