title: Mesenchymal stem cells improves survival in LPS-induced acute lung injury acting through inhibition of NETs formation.
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.
authors.affiliation: Laboratório de Pesquisa em Biofísica Celular e Inflamação, Pontifícia Universidade Católica do Rio Grande do Sul (PUCRS), Porto Alegre, Rio Grande do Sul, Brazil.
authors.forename: Leonardo
authors.initials: L
authors.lastname: Pedrazza
authors.affiliation: Laboratório de Respirologia Pediátrica, Centro Infant, Instituto de Pesquisas Biomédicas (IPB), Pontifícia Universidade Católica do Rio Grande do Sul (PUCRS), Porto Alegre, Rio Grande do Sul, Brazil.
authors.forename: Aline Andrea
authors.initials: AA
authors.lastname: Cunha
authors.affiliation: Laboratório de Pesquisa em Biofísica Celular e Inflamação, Pontifícia Universidade Católica do Rio Grande do Sul (PUCRS), Porto Alegre, Rio Grande do Sul, Brazil.|Laboratório de Respirologia Pediátrica, Centro Infant, Instituto de Pesquisas Biomédicas (IPB), Pontifícia Universidade Católica do Rio Grande do Sul (PUCRS), Porto Alegre, Rio Grande do Sul, Brazil.
authors.forename: Carolina
authors.initials: C
authors.lastname: Luft
authors.affiliation: Laboratório de Respirologia Pediátrica, Centro Infant, Instituto de Pesquisas Biomédicas (IPB), Pontifícia Universidade Católica do Rio Grande do Sul (PUCRS), Porto Alegre, Rio Grande do Sul, Brazil.
authors.forename: Nailê Karine
authors.initials: NK
authors.lastname: Nunes
authors.affiliation: Laboratório de Neuroproteção e Doenças Metabólicas, Departamento de Bioquímica, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil.
authors.forename: Felipe
authors.initials: F
authors.lastname: Schimitz
authors.affiliation: Instituto do Cérebro (INSCER), Pontifícia Universidade Católica do Rio Grande do Sul (PUCRS), Porto Alegre, RS, Brazil.
authors.forename: Rodrigo Benedetti
authors.initials: RB
authors.lastname: Gassen
authors.affiliation: Laboratório de Imunologia Celular e Molecular, Instituto de Pesquisas Biomédicas (IPB), Pontifícia Universidade Católica do Rio Grande do Sul (PUCRS), Porto Alegre, Rio Grande do Sul, Brazil.
authors.forename: Ricardo Vaz
authors.initials: RV
authors.lastname: Breda
authors.affiliation: Laboratório de Pesquisa em Biofísica Celular e Inflamação, Pontifícia Universidade Católica do Rio Grande do Sul (PUCRS), Porto Alegre, Rio Grande do Sul, Brazil.|Laboratório de Respirologia Pediátrica, Centro Infant, Instituto de Pesquisas Biomédicas (IPB), Pontifícia Universidade Católica do Rio Grande do Sul (PUCRS), Porto Alegre, Rio Grande do Sul, Brazil.
authors.forename: Marcio Vinícius Fagundes
authors.initials: MV
authors.lastname: Donadio
authors.affiliation: Laboratório de Neuroproteção e Doenças Metabólicas, Departamento de Bioquímica, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil.
authors.forename: Angela Terezinha
authors.initials: AT
authors.lastname: de Souza Wyse
authors.affiliation: Laboratório de Respirologia Pediátrica, Centro Infant, Instituto de Pesquisas Biomédicas (IPB), Pontifícia Universidade Católica do Rio Grande do Sul (PUCRS), Porto Alegre, Rio Grande do Sul, Brazil.
authors.forename: Paulo Marcio Condessa
authors.initials: PMC
authors.lastname: Pitrez
authors.affiliation: Departament de Ciències Fisiològiques, IDIBELL, Campus de Bellvitge, Universitat de Barcelona, L'Hospitalet de Llobregat, Barcelona, Spain.
authors.forename: Jose Luis
authors.initials: JL
authors.lastname: Rosa
authors.affiliation: Laboratório de Pesquisa em Biofísica Celular e Inflamação, Pontifícia Universidade Católica do Rio Grande do Sul (PUCRS), Porto Alegre, Rio Grande do Sul, Brazil.
authors.forename: Jarbas Rodrigues
authors.initials: JR
authors.lastname: de Oliveira
mesh_terms: D055371:Acute Lung Injury / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology / Q000601:surgery*; D000818:Animals; D002478:Cells, Cultured; D002633:Chemotaxis; D051546:Cyclooxygenase 2 / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D065206:Extracellular Traps / Q000378:metabolism*; D018836:Inflammation Mediators / Q000378:metabolism; D008070:Lipopolysaccharides; D008168:Lung / Q000378:metabolism* / Q000473:pathology; D008264:Macrophages / Q000378:metabolism / Q000473:pathology; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation; D008810:Mice, Inbred C57BL; D016328:NF-kappa B / Q000378:metabolism; D020556:Neutrophil Infiltration; D009504:Neutrophils / Q000378:metabolism / Q000473:pathology; D018384:Oxidative Stress; D011014:Pneumonia / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology / Q000601:surgery*; D013997:Time Factors
chemical_list: D016207:Cytokines; D018836:Inflammation Mediators; D008070:Lipopolysaccharides; D016328:NF-kappa B; C433788:lipopolysaccharide, E. coli O26-B6; C077623:Ptgs2 protein, mouse; D051546:Cyclooxygenase 2
keywords: acute lung injury; inflammation; mesenchymal stem cells; neutrophil extracellular traps; oxidative stress