Reactive-oxygen-species-mediated P. aeruginosa killing is functional in human cystic fibrosis macrophages.
Reactive-oxygen-species-mediated P. aeruginosa killing is functional in human cystic fibrosis macrophages.
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DOI：
10.1371/journal.pone.0071717
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Del Porto P
中科院分区：
文献类型：
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作者：
Cifani N;Pompili B;Anile M;Patella M;Diso D;Venuta F;Cimino G;Quattrucci S;Di Domenico EG;Ascenzioni F;Del Porto P
铜绿假单胞菌是囊性纤维化（CF）患者慢性肺部感染最常见的病原体。约80%的成年CF患者患有慢性铜绿假单胞菌感染，这占了大部分的发病率和大部分的死亡率。细菌的遗传适应和先天免疫反应缺陷都有助于细菌的持久性。CF跨膜传导调节因子（CFTR）功能障碍损害气道上皮介导的肺防御是公认的;然而，其他先天免疫细胞也似乎受到影响，如中性粒细胞和巨噬细胞，因此有助于CF肺中的这种感染性病理。在巨噬细胞中，CFTR的缺乏与缺陷性铜绿假单胞菌杀伤、促炎细胞因子分泌增加和活性氧（ROS）产生减少有关。为了更多地了解CF患者中的巨噬细胞功能障碍，我们研究了铜绿假单胞菌感染后，从CF患者的外周血或肺实质分离的CF巨噬细胞中氧化爆发的产生及其对细菌杀伤的影响。我们的数据表明，CF巨噬细胞显示出与非CF巨噬细胞相似强度的氧化反应。细胞内活性氧被认为是最早的杀微生物机制之一，针对吞噬的病原体，由巨噬细胞激活。因此，NADPH抑制导致CF和非CF巨噬细胞（作为单核细胞衍生的巨噬细胞和肺巨噬细胞）中细胞内细菌存活的显著增加。这些数据强烈表明ROS对铜绿假单胞菌杀伤的贡献不受CFTR突变的影响。
Pseudomonas aeruginosa is the most common pathogen for chronic lung infection in cystic fibrosis (CF) patients. About 80% of adult CF patients have chronic P. aeruginosa infection, which accounts for much of the morbidity and most of the mortality. Both bacterial genetic adaptations and defective innate immune responses contribute to the bacteria persistence. It is well accepted that CF transmembrane conductance regulator (CFTR) dysfunction impairs the airways-epithelium-mediated lung defence; however, other innate immune cells also appear to be affected, such as neutrophils and macrophages, which thus contribute to this infectious pathology in the CF lung. In macrophages, the absence of CFTR has been linked to defective P. aeruginosa killing, increased pro-inflammatory cytokine secretion, and reduced reactive oxygen species (ROS) production. To learn more about macrophage dysfunction in CF patients, we investigated the generation of the oxidative burst and its impact on bacterial killing in CF macrophages isolated from peripheral blood or lung parenchyma of CF patients, after P. aeruginosa infection. Our data demonstrate that CF macrophages show an oxidative response of similar intensity to that of non-CF macrophages. Intracellular ROS are recognized as one of the earliest microbicidal mechanisms against engulfed pathogens that are activated by macrophages. Accordingly, NADPH inhibition resulted in a significant increase in the intracellular bacteria survival in CF and non-CF macrophages, both as monocyte-derived macrophages and as lung macrophages. These data strongly suggest that the contribution of ROS to P. aeruginosa killing is not affected by CFTR mutations.
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影响因子：
30.8
作者：
Rozmahel, R;Wilschanski, M;Tsui, LC
通讯作者：
Tsui, LC
影响因子：
24.3
作者：
McKeon, D. J.;Cadwallader, K. A.;Condliffe, A. M.
通讯作者：
Condliffe, A. M.
DOI：
10.1164/ajrccm.150.1.7912987
发表时间：
1994-07-01
影响因子：
24.7
作者：
BIRRER, P;MCELVANEY, NG;CRYSTAL, RG
通讯作者：
CRYSTAL, RG
影响因子：
5.1
作者：
Auriche, C.;Di Domenico, E. G.;Ascenzioni, F.
通讯作者：
Ascenzioni, F.
影响因子：
82.9
作者：
通讯作者：
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