Human mesenchymal stem cells reduce mortality and bacteremia in gram-negative sepsis in mice in part by enhancing the phagocytic activity of blood monocytes
Human mesenchymal stem cells reduce mortality and bacteremia in gram-negative sepsis in mice in part by enhancing the phagocytic activity of blood monocytes
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DOI：
10.1152/ajplung.00180.2011
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发表时间：
2012-05-01
影响因子：
4.9
通讯作者：
Matthay, Michael A.
中科院分区：
文献类型：
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作者：
Krasnodembskaya, Anna;Samarani, Gianluca;Matthay, Michael A.
Krasnodembskaya A，Samarani G，Song Y，卓H，Su X，Lee JW，Gupta N，Petrini M，Matthay MA。人类间充质干细胞减少革兰氏阴性败血症小鼠的死亡率和菌血症，部分是通过增强单核细胞的吞噬活性。Am J Physiol肺细胞分子Physiol 302：L1003-L1013,2012。2012年3月16日首次出版；DOI：10.1152/ajpeng.00180.2011。-间充质干细胞(MSCs)基于细胞的治疗在多菌腹膜败血症小鼠模型中的潜在治疗价值已被报道。然而，对MSC的有益作用的机制还没有很好的定义。因此，我们检测了静脉注射人骨髓间充质干细胞对革兰氏阴性菌所致的腹膜脓毒症的治疗效果。48小时后，静脉注射MSC的小鼠的存活率显著高于静脉注射成纤维细胞(3T3)或静脉注射PBS的对照组小鼠。两组患者血浆中肿瘤坏死因子-α、巨噬细胞炎性蛋白-2和IL-10水平无显著差异。然而，与3T3和PBS对照组相比，MSC处理组小鼠血液中铜绿假单胞菌的细菌集落形成单位显著减少。此外，与3T3和PBS组相比，经MSC处理的小鼠外周血单核细胞的吞噬活性增加。此外，接受MSC治疗的小鼠血液中C5a过敏毒素水平升高，这一发现与单核细胞吞噬受体CD11b上调有关。中性粒细胞吞噬功能组间差异无统计学意义。与两个对照组相比，接受MSC治疗的小鼠脾中交替激活的单核/巨噬细胞(CD163和CD206阳性)也增加。因此，静脉注射MSC提高了革兰氏阴性腹膜败血症的存活率，部分是通过单核细胞依赖的细菌吞噬功能的增加。
Krasnodembskaya A, Samarani G, Song Y, Zhuo H, Su X, Lee JW, Gupta N, Petrini M, Matthay MA. Human mesenchymal stem cells reduce mortality and bacteremia in gram-negative sepsis in mice in part by enhancing the phagocytic activity of blood monocytes. Am J Physiol Lung Cell Mol Physiol 302: L1003-L1013, 2012. First published March 16, 2012; doi:10.1152/ajplung.00180.2011.-The potential therapeutic value of cell-based therapy with mesenchymal stem cells (MSC) has been reported in mouse models of polymicrobial peritoneal sepsis. However, the mechanisms responsible for the beneficial effects of MSC have not been well defined. Therefore, we tested the therapeutic effect of intravenous bone marrow-derived human MSC in peritoneal sepsis induced by gram-negative bacteria. At 48 h, survival was significantly increased in mice treated with intravenous MSC compared with control mice treated with intravenous fibroblasts (3T3) or intravenous PBS. There were no significant differences in the levels of TNF-alpha, macrophage inflammatory protein 2, or IL-10 in the plasma. However, there was a marked reduction in the number of bacterial colony-forming units of Pseudomonas aeruginosa in the blood of MSC-treated mice compared with the 3T3 and PBS control groups. In addition, phagocytic activity was increased in blood monocytes isolated from mice treated with MSC compared with the 3T3 and PBS groups. Furthermore, levels of C5a anaphylotoxin were elevated in the blood of mice treated with MSC, a finding that was associated with upregulation of the phagocytosis receptor CD11b on monocytes. The phagocytic activity of neutrophils was not different among the groups. There was also an increase in alternately activated monocytes/macrophages (CD163- and CD206-positive) in the spleen of the MSC-treated mice compared with the two controls. Thus intravenous MSC increased survival from gram-negative peritoneal sepsis, in part by a monocyte-dependent increase in bacterial phagocytosis.