Impaired ability of Cftr knockout mice to control lung infection with Pseudomonas aeruginosa

Impaired ability of Cftr knockout mice to control lung infection with Pseudomonas aeruginosa
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DOI:
10.1164/ajrccm.157.4.9702081
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发表时间:
1998-04-01
影响因子:
24.7
通讯作者:
Radzioch, D
Radzioch, D
中科院分区:
医学1区
文献类型:
--
作者:
Gosselin, D;Stevenson, MM;Radzioch, D

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本研究旨在探讨C57 BL/6-Cftr(unc)/Cftr(unc)基因敲除小鼠对铜绿假单胞菌肺部感染的先天易感性。我们的研究结果表明,58.4%的B6-Cftr(-/-)小鼠在肺部感染10(5)株包埋在琼脂珠中的铜绿假单胞菌后6天内死亡,而在同一时间段内,只有12.1%的B6-Cftr(+/+)小鼠死亡。此外,从B6-Cftr(-/-)小鼠感染后3和6天的肺部回收的细菌数量显着高于其同窝对照组中观察到的数量。在动物的体重或年龄与从小鼠肺中回收的活细菌数量之间没有发现相关性。对铜绿假单胞菌感染小鼠的肺切片进行的组织学检查显示,感染导致严重的支气管扩张症。在感染过程中,B6-Cftr(-/-)基因敲除小鼠及其同窝对照小鼠均出现了相似的肺部病理学。总体而言,本研究中报告的结果表明,Cftr基因座的缺陷导致铜绿假单胞菌肺部感染加重,导致死亡率显著增加和细菌负荷增加。
The present study was aimed at investigating the innate susceptibility of C57BL/6-Cftr(unc)/Cftr(unc) knockout [B6-Cftr(-/-)] mice to pulmonary infection with Pseudomonas aeruginosa. Our results indicate that 58.4% of B6-Cftr(-/-) mice died within 6 d following lung infection with 10(5) P. aeruginosa entrapped in agar beads, whereas only 12.1% of B6-Cftr (+/+) mice died over the same period of time. Moreover, the number of bacteria recovered from the lungs of B6-Cftr(-/-) mice 3 and 6 d after infection was significantly higher than that observed in their littermate controls. No correlation was found between the weight or age of the animals and the number of viable bacteria recovered from the lungs of mice. Histopathological examination of lung sections from P. aeruginosa-infected mice revealed that the infection results in a severe bronchopneumonia. Both B6-Cftr(-/-) knockout mice and their littermate controls developed similar lung pathology during the course of infection. Overall, results reported in the present study suggest that a defect at the Cftr locus leads to an exacerbation of P. aeruginosa lung infection resulting in a dramatically increased mortality rate and higher bacterial load.