Mesenchymal stem cells improves survival in LPS-induced acute lung injury acting through inhibition of NETs formation
Mesenchymal stem cells improves survival in LPS-induced acute lung injury acting through inhibition of NETs formation
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DOI：
10.1002/jcp.25816
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发表时间：
2017-12-01
影响因子：
5.6
通讯作者：
de Oliveira, Jarbas Rodrigues
中科院分区：
文献类型：
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作者：
Pedrazza, Leonardo;Cunha, Aline Andrea;de Oliveira, Jarbas Rodrigues
急性肺损伤(ALI)和急性呼吸窘迫综合征(ARDS)是急性低氧性呼吸衰竭的综合征，由各种直接和间接的肺气体交换实质损伤引起。在ALI过程中，促炎症细胞因子的释放增加，并形成高活性氧(ROS)。这些因素负责中性粒细胞衍生的蛋白酶的释放和激活，以及中性粒细胞胞外陷阱(Net)的形成。过度增加的Net释放会对肺组织造成损害。最近的研究涉及到应用间充质干细胞(MSCs)治疗实验性ALI，结果令人振奋。通过这种方式，我们的研究目的是评估MSCs在脂多糖(LPS)诱导的ALI模型中减轻炎症和氧化损伤的能力，从而减少Net的释放。小鼠气管内注入脂多糖造成肺损伤，随后给予MSCs治疗或不给予MSCs治疗。MSCs治疗能够调节肺部炎症，减少氧化损伤，并减少Net的释放。当我们观察到接受治疗的动物的存活曲线显著增加时，这些治疗的好处是显而易见的。结果表明，MSCs治疗ALI是有效的。首次描述了MSCs可减少Net的形成，并建立了ALI的实验模型。这一发现与这些细胞在病理过程中调节炎症反应和氧化损伤有直接关系。
Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are syndromes of acute hypoxemic respiratory failure resulting from a variety of direct and indirect injuries to the gas exchange parenchyma of the lungs. During the ALI, we have an increase release of proinflammatory cytokines and high reactive oxygen species (ROS) formation. These factors are responsible for the release and activation of neutrophil-derived proteases and the formation of neutrophil extracellular traps (NETs). The excessive increase in the release of NETs cause damage to lung tissue. Recent studies have studies involving the administration of mesenchymal stem cells (MSCs) for the treatment of experimental ALI has shown promising results. In this way, the objective of our study is to evaluate the ability of MSCs, in a lipopolysaccharide (LPS)-induced ALI model, to reduce inflammation, oxidative damage, and consequently decrease the release of NETs. Mice were submitted lung injury induced by intratracheal instillation of LPS and subsequently treated or not with MSCs. Treatment with MSCs was able to modulate pulmonary inflammation, decrease oxidative damage, and reduce the release of NETs. These benefits from treatment are evident when we observe a significant increase in the survival curve in the treated animals. Our results demonstrate that MSCs treatment is effective for the treatment of ALI. For the first time, it is described that MSCs can reduce the formation of NETs and an experimental model of ALI. This finding is directly related to these cells modulate the inflammatory response and oxidative damage in the course of the pathology.