1. Mesenchymal stem cells improves survival in LPS-induced acute lung injury acting through inhibition of NETs formation.
- Author
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Pedrazza L, Cunha AA, Luft C, Nunes NK, Schimitz F, Gassen RB, Breda RV, Donadio MV, de Souza Wyse AT, Pitrez PMC, Rosa JL, and de Oliveira JR
- Subjects
- Acute Lung Injury chemically induced, Acute Lung Injury metabolism, Acute Lung Injury pathology, Animals, Cells, Cultured, Chemotaxis, Cyclooxygenase 2 metabolism, Cytokines metabolism, Disease Models, Animal, Inflammation Mediators metabolism, Lipopolysaccharides, Lung pathology, Macrophages metabolism, Macrophages pathology, Male, Mice, Inbred C57BL, NF-kappa B metabolism, Neutrophil Infiltration, Neutrophils metabolism, Neutrophils pathology, Oxidative Stress, Pneumonia chemically induced, Pneumonia metabolism, Pneumonia pathology, Time Factors, Acute Lung Injury surgery, Extracellular Traps metabolism, Lung metabolism, Mesenchymal Stem Cell Transplantation, Pneumonia surgery
- Abstract
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., (© 2017 Wiley Periodicals, Inc.)
- Published
- 2017
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