Mesenchymal stem cells enhance survival and bacterial clearance in murine Escherichia coli pneumonia.
Mesenchymal stem cells enhance survival and bacterial clearance in murine Escherichia coli pneumonia.
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DOI：
10.1136/thoraxjnl-2011-201176
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发表时间：
2012-06
期刊：
影响因子：
10
通讯作者：
Matthay MA
中科院分区：
文献类型：
--
作者：
Gupta N;Krasnodembskaya A;Kapetanaki M;Mouded M;Tan X;Serikov V;Matthay MA
细菌性肺炎是全世界最常见的感染性死亡原因，抗生素耐药性越来越阻碍治疗。间充质干细胞(MSCs)已被证明对急性炎症性肺损伤具有保护作用，但其在细菌性肺炎中的潜在治疗作用尚未得到很好的研究。本研究的重点是测试骨髓间充质干细胞在革兰氏阴性肺炎小鼠模型中的治疗和机制作用。从野生型小鼠体内分离出同基因的MSCs，在感染大肠杆菌后4h经气管内给药。以3T3成纤维细胞和磷酸盐缓冲液(PBS)为对照进行体内实验。测定各治疗组的存活率、肺损伤、细菌计数和炎症指数。与对照组相比，野生型MSCs组小鼠的48h存活率(MSC组为55%；3T3组为8%；PBS组为0；PBS组为0；P<；0.05)和肺损伤程度均有所改善。此外，野生型MSCs在给药后4h就能促进细菌从肺泡腔中清除，这是其他治疗组没有观察到的效果。MSCs的抗菌作用部分是由于它们上调了抗菌蛋白Lipocalin 2。MSCs治疗提高了革兰氏阴性肺炎小鼠的存活率和细菌清除率。细菌清除作用的部分原因是MSCs上调了Lipocalin 2的产生。
Bacterial pneumonia is the most common infectious cause of death worldwide and treatment is increasingly hampered by antibiotic resistance. Mesenchymal stem cells (MSCs) have been demonstrated to provide protection against acute inflammatory lung injury; however, their potential therapeutic role in the setting of bacterial pneumonia has not been well studied. This study focused on testing the therapeutic and mechanistic effects of MSCs in a mouse model of Gram-negative pneumonia. Syngeneic MSCs from wild-type mice were isolated and administered via the intratracheal route to mice 4 h after the mice were infected with Escherichia coli. 3T3 fibroblasts and phosphate-buffered saline (PBS) were used as controls for all in vivo experiments. Survival, lung injury, bacterial counts and indices of inflammation were measured in each treatment group. Treatment with wild-type MSCs improved 48 h survival (MSC, 55%; 3T3, 8%; PBS, 0%; p<0.05 for MSC vs 3T3 and PBS groups) and lung injury compared with control mice. In addition, wild-type MSCs enhanced bacterial clearance from the alveolar space as early as 4 h after administration, an effect that was not observed with the other treatment groups. The antibacterial effect with MSCs was due, in part, to their upregulation of the antibacterial protein lipocalin 2. Treatment with MSCs enhanced survival and bacterial clearance in a mouse model of Gram-negative pneumonia. The bacterial clearance effect was due, in part, to the upregulation of lipocalin 2 production by MSCs.
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影响因子：
4.4
作者：
Su, Xiao;Johansen, Mette;Matthay, Michael A.
通讯作者：
Matthay, Michael A.
影响因子：
5.8
作者：
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82.9
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影响因子：
4.4
作者：
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通讯作者：
Borregaard, Niels
影响因子：
4.4
作者：
Gupta, Naveen;Su, Xiao;Matthay, Michael A.
通讯作者：
Matthay, Michael A.