Electroporation-mediated delivery of the FER gene in the resolution of trauma-related fatal pneumonia.
Electroporation-mediated delivery of the FER gene in the resolution of trauma-related fatal pneumonia.
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DOI：
10.1038/gt.2016.58
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发表时间：
2016-11
期刊：
影响因子：
5.1
通讯作者：
Machado-Aranda, D.
中科院分区：
文献类型：
--
作者：
Dolgachev, V. A.;Goldberg, R.;Suresh, M. V.;Thomas, B.;Talarico, N.;Hemmila, M. R.;Raghavendran, K.;Machado-Aranda, D.
肺挫伤（LC）的受伤患者有发生细菌性肺炎（PNA）的风险，随后是败血症和死亡。最近的一项全基因组关联研究显示，FER基因表达与上述疾病患者的生存率呈正相关。我们试图确定是否电穿孔介导（EP）的FER基因的交付确实可以提高生存，在一个致命的模型相结合的LC和PNA。C57 BL/6小鼠持续单侧LC，其在500克雷伯氏菌CFU接种之前6小时。在这些损伤之间，将人FER质粒（pFER）引入肺中，随后外部施加8个EP脉冲（10 ms，200 V/cm）。对照组包括空载体（pcDNA 3）或Na+/K+-ATP酶基因（pPump）的EP和不处理（LC + PNA）。我们记录了存活率、组织学、肺力学、支气管肺泡液（BAL）、FER和炎症基因表达以及细菌学。数据显示，与对照组相比，pFER显著改善了7天存活率。pFER可增加BAL单核细胞数量，激活抗菌反应基因（NOS，Fizz）。pFER治疗显示肺和血液克雷伯氏菌计数降低，在某些情况下达到完全灭菌。总之，FER基因递送通过募集活化的免疫细胞来促进LC+PNA小鼠的存活，提高挫伤肺内细菌清除效率
Injured patients with lung contusion (LC) are at risk of developing bacterial pneumonia (PNA) followed by sepsis and death. A recent Genome-wide Association Study, showed FER gene expression positively correlating with survival rates among individuals with above conditions. We sought to determine if electroporation-mediated (EP) delivery of FER gene could indeed improve survival, in a lethal model of combined LC and PNA. C57BL/6 mice sustained unilateral LC, which preceded a 500 Klebsiella CFU inoculation by 6 hrs. In-between these insults, human FER plasmid (pFER) was introduced into the lungs followed by eight EP pulses applied externally (10ms at 200V/cm). Control groups included EP of empty vector (pcDNA3) or Na+/K+-ATPase genes (pPump) and no treatment (LC + PNA). We recorded survival, histology, lung mechanics, bronchial alveolar fluid (BAL), FER and inflammatory gene expression and bacteriology. The data shows that 7-day survival was significantly improved by pFER compared to control groups. pFER increased BAL monocytes and activated antibacterial response genes (NOS, Fizz). pFER treatment showed decreased lung and blood Klebsiella counts reaching, in some cases, complete sterilization. In conclusion, FER gene delivery promoted survival in LC+PNA mice via recruitment of activated immune cells, improving efficiency of bacterial clearance within contused lung
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影响因子：
3.1
作者：
Emr, Bryanna M.;Roy, Shreyas;Dean, David A.
通讯作者：
Dean, David A.
影响因子：
3.8
作者：
Machado-Aranda, David;Wang, Zhengdong;Yu, Bi;Suresh, M. V.;Notter, Robert H.;Raghavendran, Krishnan
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影响因子：
5.5
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5.2
作者：
Ahn, Joseph;Truesdell, Peter;Craig, Andrew W. B.
通讯作者：
Craig, Andrew W. B.
影响因子：
5.3
作者：
HAO, QL;HEISTERKAMP, N;GROFFEN, J
通讯作者：
GROFFEN, J