Cystic fibrosis sputum DNA has NETosis characteristics and neutrophil extracellular trap release is regulated by macrophage migration-inhibitory factor.
Cystic fibrosis sputum DNA has NETosis characteristics and neutrophil extracellular trap release is regulated by macrophage migration-inhibitory factor.
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DOI：
10.1159/000363242
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发表时间：
2014
影响因子：
5.3
通讯作者：
Gadjeva M
中科院分区：
文献类型：
--
作者：
Dwyer M;Shan Q;D'Ortona S;Maurer R;Mitchell R;Olesen H;Thiel S;Huebner J;Gadjeva M
中性粒细胞是囊性纤维化患者肺部慢性感染的主要致炎细胞类型，但不能有效清除定植病原体。在这里，我们研究了非粘液性和粘液性铜绿假单胞菌在体外诱导的Net的分子组成，并将它们与CF痰中存在的DNA-蛋白质复合体进行了比较。铜绿假单胞菌诱导的Net片段的蛋白质组成表明，无论诱导刺激如何，Net片段上都装饰着一组保守的蛋白质。从CF痰中提取的DNA-蛋白质复合体与NETsis一致，并具有相似的蛋白质特征，表明大多数细胞外DNA是净源的。巨噬细胞移动抑制因子(MIF)通过促进MAPK的激活来促进PMN对铜绿假单胞菌产生Net的能力。对132例CF患者样本的分析表明，MIF蛋白水平升高与肺功能较差相关。我们认为，通过小分子抑制剂靶向MIF可能会减少细胞外DNA(EDNA)的存在，并作为抗菌药物使用的辅助手段，这些药物最终可能会降低CF病后期肺部的细菌适应性。
Neutrophils are the main proinflammatory cell type in the chronically infected lungs of the Cystic Fibrosis (CF) patients, however they fail to effectively clear the colonizing pathogens. Here, we investigated the molecular composition of non-mucoid and mucoid P. aeruginosa-induced NETs in vitro and compared them to the DNA-protein complexes present in the CF sputum. The protein composition of P. aeruginosa-induced NET fragments revealed that irrespective of the inducing stimuli, NET fragments were decorated with a conserved set of proteins. The DNA-protein complexes derived from CF sputum were consistent with NETosis and shared a similar protein signature, suggesting that the majority of the extracellular DNA was NET-derived. The ability of the PMNs to produce NETs in response to P. aeruginosa was driven by Macrophage Migration Inhibitory Factor (MIF) by promoting MAPK activation. Analysis of 132 CF patient samples revealed that elevated MIF protein levels correlated with poorer lung function. We suggest that targeting MIF by small molecular inhibitors might reduce the extracellular DNA (eDNA) presence and serve as an adjunct to the use of antimicrobial drugs that could ultimately reduce bacterial fitness in the lungs during the later stages of CF disease.
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DOI：
10.1084/jem.20100239
发表时间：
2010-08-30
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Li P;Li M;Lindberg MR;Kennett MJ;Xiong N;Wang Y
通讯作者：
Wang Y
DOI：
10.1073/pnas.0701553104
发表时间：
2007-08-14
影响因子：
11.1
作者：
Binsky, Inbal;Haran, Michal;Shachar, Idit
通讯作者：
Shachar, Idit
DOI：
10.1165/rcmb.2011-0380oc
发表时间：
2012-07-01
影响因子：
6.4
作者：
Dubois, Alice V.;Gauthier, Alexandre;Attucci, Sylvie
通讯作者：
Attucci, Sylvie
影响因子：
5.5
作者：
Parker, Heather;Albrett, Amelia M.;Winterbourn, Christine C.
通讯作者：
Winterbourn, Christine C.
DOI：
10.1073/pnas.1221817110
发表时间：
2013-07-02
影响因子：
11.1
作者：
Fan, Chengpeng;Rajasekaran, Deepa;Lolis, Elias J.
通讯作者：
Lolis, Elias J.