Mesenchymal stem cells improves survival in LPS‐induced acute lung injury acting through inhibition of NETs formation

急性呼吸窘迫综合征 间充质干细胞 促炎细胞因子 炎症 医学 薄壁组织 脂多糖 免疫学 氧化应激 中性粒细胞胞外陷阱 药理学 病理 内科学
作者
Leonardo Pedrazza,Aline Andrea da Cunha,Carolina Luft,Nailê Karine Nunes,Felipe Schimitz,Rodrigo Benedetti Gassen,Ricardo Vaz Breda,Márcio Vinı́cius Fagundes Donadio,Ângela T. S. Wyse,Paulo Márcio Pitrez,José Luís Rosa,Jarbas Rodrigues de Oliveira
出处
期刊:Journal of Cellular Physiology [Wiley]
卷期号:232 (12): 3552-3564 被引量:71
标识
DOI:10.1002/jcp.25816
摘要

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.

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