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Early and late pulmonary effects of nebulized LPS in mice: An acute lung injury model
BACKGROUND AND OBJECTIVE: Acute respiratory distress syndrome (ARDS) has a high mortality rate of 35–46% depending on its severity. Animal models are crucial to better understand the pathophysiology of diseases, including ARDS. This study presents a feasible animal model of acute lung injury (ALI) u...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5617199/ https://www.ncbi.nlm.nih.gov/pubmed/28953963 http://dx.doi.org/10.1371/journal.pone.0185474 |
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author | de Souza Xavier Costa, Natália Ribeiro Júnior, Gabriel dos Santos Alemany, Adair Aparecida Belotti, Luciano Zati, Douglas Hidalgo Frota Cavalcante, Marcela Matera Veras, Mariana Ribeiro, Susan Kallás, Esper Georges Nascimento Saldiva, Paulo Hilário Dolhnikoff, Marisa Ferraz da Silva, Luiz Fernando |
author_facet | de Souza Xavier Costa, Natália Ribeiro Júnior, Gabriel dos Santos Alemany, Adair Aparecida Belotti, Luciano Zati, Douglas Hidalgo Frota Cavalcante, Marcela Matera Veras, Mariana Ribeiro, Susan Kallás, Esper Georges Nascimento Saldiva, Paulo Hilário Dolhnikoff, Marisa Ferraz da Silva, Luiz Fernando |
author_sort | de Souza Xavier Costa, Natália |
collection | PubMed |
description | BACKGROUND AND OBJECTIVE: Acute respiratory distress syndrome (ARDS) has a high mortality rate of 35–46% depending on its severity. Animal models are crucial to better understand the pathophysiology of diseases, including ARDS. This study presents a feasible animal model of acute lung injury (ALI) using nebulized lipopolysaccharide (LPS) in a non-invasive approach, focusing on its short and long-term effects. METHODS: Mice received nebulized LPS or vehicle only (control group). Blood, BALF and lung tissue were collected 24 hours (LPS 24h) or 5 weeks (LPS 5w) after the nebulized LPS-induced lung injury. Inflammatory cytokines were assessed in the blood serum, BALF and lung tissue. Stereological analyses and remodeling changes were assessed by histology and immunohistochemistry at the specified time points. RESULTS: The LPS 24h group showed increased pro-inflammatory cytokine levels, intense cell influx, increased total septal volume, septal thickening and decreased surface density of the alveolar septa. The LPS 5w group showed persistent lung inflammation, septal thickening, increased total lung volume, accentuated collagen deposition, especially of collagen type I, and decreased MMP-2 protein expression. CONCLUSION: We present a feasible, reproducible and non-invasive nebulized-LPS animal model that allows the assessment of both the acute and late phases of acute lung injury. The presence of lung remodeling with collagen deposition after 5 weeks makes it useful to study the pathophysiology, complications, and possible therapeutic intervention studies that aim to understand and reduce pulmonary fibrosis in the late phases of ALI. |
format | Online Article Text |
id | pubmed-5617199 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-56171992017-10-09 Early and late pulmonary effects of nebulized LPS in mice: An acute lung injury model de Souza Xavier Costa, Natália Ribeiro Júnior, Gabriel dos Santos Alemany, Adair Aparecida Belotti, Luciano Zati, Douglas Hidalgo Frota Cavalcante, Marcela Matera Veras, Mariana Ribeiro, Susan Kallás, Esper Georges Nascimento Saldiva, Paulo Hilário Dolhnikoff, Marisa Ferraz da Silva, Luiz Fernando PLoS One Research Article BACKGROUND AND OBJECTIVE: Acute respiratory distress syndrome (ARDS) has a high mortality rate of 35–46% depending on its severity. Animal models are crucial to better understand the pathophysiology of diseases, including ARDS. This study presents a feasible animal model of acute lung injury (ALI) using nebulized lipopolysaccharide (LPS) in a non-invasive approach, focusing on its short and long-term effects. METHODS: Mice received nebulized LPS or vehicle only (control group). Blood, BALF and lung tissue were collected 24 hours (LPS 24h) or 5 weeks (LPS 5w) after the nebulized LPS-induced lung injury. Inflammatory cytokines were assessed in the blood serum, BALF and lung tissue. Stereological analyses and remodeling changes were assessed by histology and immunohistochemistry at the specified time points. RESULTS: The LPS 24h group showed increased pro-inflammatory cytokine levels, intense cell influx, increased total septal volume, septal thickening and decreased surface density of the alveolar septa. The LPS 5w group showed persistent lung inflammation, septal thickening, increased total lung volume, accentuated collagen deposition, especially of collagen type I, and decreased MMP-2 protein expression. CONCLUSION: We present a feasible, reproducible and non-invasive nebulized-LPS animal model that allows the assessment of both the acute and late phases of acute lung injury. The presence of lung remodeling with collagen deposition after 5 weeks makes it useful to study the pathophysiology, complications, and possible therapeutic intervention studies that aim to understand and reduce pulmonary fibrosis in the late phases of ALI. Public Library of Science 2017-09-27 /pmc/articles/PMC5617199/ /pubmed/28953963 http://dx.doi.org/10.1371/journal.pone.0185474 Text en © 2017 de Souza Xavier Costa et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Article de Souza Xavier Costa, Natália Ribeiro Júnior, Gabriel dos Santos Alemany, Adair Aparecida Belotti, Luciano Zati, Douglas Hidalgo Frota Cavalcante, Marcela Matera Veras, Mariana Ribeiro, Susan Kallás, Esper Georges Nascimento Saldiva, Paulo Hilário Dolhnikoff, Marisa Ferraz da Silva, Luiz Fernando Early and late pulmonary effects of nebulized LPS in mice: An acute lung injury model |
title | Early and late pulmonary effects of nebulized LPS in mice: An acute lung injury model |
title_full | Early and late pulmonary effects of nebulized LPS in mice: An acute lung injury model |
title_fullStr | Early and late pulmonary effects of nebulized LPS in mice: An acute lung injury model |
title_full_unstemmed | Early and late pulmonary effects of nebulized LPS in mice: An acute lung injury model |
title_short | Early and late pulmonary effects of nebulized LPS in mice: An acute lung injury model |
title_sort | early and late pulmonary effects of nebulized lps in mice: an acute lung injury model |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5617199/ https://www.ncbi.nlm.nih.gov/pubmed/28953963 http://dx.doi.org/10.1371/journal.pone.0185474 |
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