Lung tissue remodeling in the acute respiratory distress syndrome

Souza, Alba B.; Santos, Flávia B.; Negri, Elnara M.; Zin, Walter A.; Rocco, Patrícia Rieken Macêdo

doi:10.1590/s0102-35862003000400013

Cited by 4 publications

(3 citation statements)

References 37 publications

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“…Elastin’s intrinsic autofluorescence originates from pyridoxine-based pyridolamine cross-links [ 35 , 42 ] found primarily in mature elastin fibers [ 43 ], therefore TPEF of endogenous lung elastin preferentially identifies mature elastin fibers in lung tissue. These results are consistent with the concept that breakdown of mature elastin fibers in the lung, and their “replacement” with often excess deposition of immature elastin fibers and elastin precursors, is believed to contribute to reduced lung function in a variety of pulmonary diseases [ 49 ]. In other words, increased elastosis (i.e.…”

Section: Discussionsupporting

confidence: 90%

Second harmonic generation microscopy reveals altered collagen microstructure in usual interstitial pneumonia versus healthy lung

et al. 2015

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BackgroundIt is not understood why some pulmonary fibroses such as cryptogenic organizing pneumonia (COP) respond well to treatment, while others like usual interstitial pneumonia (UIP) do not. Increased understanding of the structure and function of the matrix in this area is critical to improving our understanding of the biology of these diseases and developing novel therapies. The objectives herein are to provide new insights into the underlying collagen- and matrix-related biological mechanisms driving COP versus UIP.MethodsTwo-photon second harmonic generation (SHG) and excitation fluorescence microscopies were used to interrogate and quantify differences between intrinsic fibrillar collagen and elastin matrix signals in healthy, COP, and UIP lung.ResultsCollagen microstructure was different in UIP versus healthy lung, but not in COP versus healthy, as indicated by the ratio of forward-to-backward propagating SHG signal (FSHG/BSHG). This collagen microstructure as assessed by FSHG/BSHG was also different in areas with preserved alveolar architecture adjacent to UIP fibroblastic foci or honeycomb areas versus healthy lung. Fibrosis was evidenced by increased col1 and col3 content in COP and UIP versus healthy, with highest col1:col3 ratio in UIP. Evidence of elastin breakdown (i.e. reduced mature elastin fiber content), and increased collagen:mature elastin ratios, were seen in COP and UIP versus healthy.ConclusionsFibrillar collagen’s subresolution structure (i.e. “microstructure”) is altered in UIP versus COP and healthy lung, which may provide novel insights into the biological reasons why unlike COP, UIP is resistant to therapies, and demonstrates the ability of SHG microscopy to potentially distinguish treatable versus intractable pulmonary fibroses.

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Section: Discussionsupporting

confidence: 90%

Second harmonic generation microscopy reveals altered collagen microstructure in usual interstitial pneumonia versus healthy lung

et al. 2015

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“…Recently, a significant proportion of patients infected with coronavirus disease-2019 (COVID-19) developed viral pneumonia that caused an acute lung injury (ALI) capable of rapid progression to viral sepsis and ARDS with a high fatality rate especially in older and comorbidities populations (4)(5)(6). The phases in the development of ARDS include the exudation stage characterized by the inflammatory cell infiltration and pulmonary edema (stage 1), the proliferation of myofibroblasts (stage 2), and extracellular matrix (ECM) over-deposited (stage 3) (7). The fibrosis process (stages 2 and 3) is rapid and occurs within 1 week (8,9).…”

Section: Introductionmentioning

confidence: 99%

Astrocytes Downregulate Inflammation in Lipopolysaccharide-Induced Acute Respiratory Distress Syndrome: Applicability to COVID-19

Izrael¹,

Molakandov²,

Revel³

et al. 2021

Front. Med.

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Background: An acute respiratory distress syndrome (ARDS) is caused by the increased amounts of pro-inflammatory cytokines and neutrophil-mediated tissue injury. To date, there is no effective treatment for the ARDS available, while the need for one is growing due to the most severe complications of the current coronavirus disease-2019 (COVID-19) pandemic. The human astrocytes (AstroRx) have shown immunomodulatory properties in the central nervous system (CNS). This study aimed to evaluate the capacity of astrocytes to decrease lung inflammation and to be applied as a treatment therapy in ARDS.Methods: First, we assessed the ability of clinical-grade AstroRx to suppress T-cell proliferation in a mixed lymphocyte reaction test. Next, we tested the therapeutical potential of AstroRx cells in a lipopolysaccharide (LPS)-based ARDS mouse model by injecting AstroRx intravenously (i.v). We determined the degree of lung injury by using a severity scoring scale of 0–2, based on the American Thoracic Society. The scoring measured the presence of neutrophils, fibrin deposits, and the thickening of alveolar walls. The state of inflammation was further assessed by quantifying the immune-cell infiltration to the bronchoalveolar lavage fluid (BALF) and by the presence of proinflammatory cytokines and chemokines in the BALF and serum.Results: We detected that AstroRx cells were capable to suppress T-cell proliferation in vitro after exposure to the mitogen concanavalin A (ConA). In vivo, AstroRx cells were able to lower the degree of lung injury in LPS-treated animals compared with the sham injected animals (P = 0.039). In this study, 30% of AstroRx treated mice showed no lung lesions (responder mice), these mice presented a steady number of eosinophils, T cells, and neutrophils comparable with the level of naïve control mice. The inflammatory cytokines and chemokines, such as TNFα, IL1b, IL-6, and CXCL1, were also kept in check in responder AstroRx-treated mice and were not upregulated as in the sham-injected mice (P < 0.05). As a result, the LPS-treated ARDS mice had a higher survival rate when they were treated with AstroRx.Conclusions: Our results demonstrate that the immunosuppressive activity of AstroRx cells support the application of AstroRx cells as a cell therapy treatment for ARDS. The immunoregulatory activity may also be a part of the mechanism of action of AstroRx reported in the amyotrophic lateral sclerosis (ALS) neurodegenerative disease.

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“…A quantidade de colágeno depositada no tecido depende da extensão da lesão celular, intensidade de proliferação dos fibroblastos, inflamação e hipoperfusão vascular que ocorrem durante a lesão pulmonar (Souza et al, 2003 Tabela 11 -Média, desvios padrão, medianas e intervalos interquartil dos grupos controle, poluição, LPS 24 horas e poluição + LPS (continuação).…”

Section: Tnf-αunclassified

Efeito da exposição ao material particulado atmosférico no desenvolvimento da lesão pulmonar aguda (LPA) induzida por LPS

Costa¹

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Agradeço a todos que, de alguma forma, contribuíram para a execução deste trabalho: Aos meus pais, Pedro e Sônia, por todas as palavras de carinho, apoio e incentivo durante todo o processo e a minha irmã, Mariana também por sempre me incentivar e por nos dar o maior presente que poderíamos ter este ano, minha sobrinha Antonella.Ao meu marido, Danilo, por todo amor, compreensão, companheirismo, incentivos, apoio, ajuda e principalmente paciência.Ao meu orientador Dr. Luiz Fernando Ferraz da Silva, a quem admiro muito, pela oportunidade de realizar meu mestrado, por todos os ensinamentos e incentivos, pela confiança depositada em mim, disponibilidade e por toda assistência durante estes anos. À Drª Mariana Matera Veras por todas as oportunidades que me propiciou desde o começo, pela confiança, pelos inúmeros ensinamentos, mas principalmente pela amizade. Aos amigos Gabriel, Luciano e Adair não só pela ajuda em todas as etapas deste projeto, mas também por todo apoio, incentivos e principalmente pela amizade de vocês. Sem vocês a execução deste trabalho seria mais difícil e com certeza muito mais chata. Aos amigos Felipe, Jéssica, Ana, Lígia e Jaqueline por sempre estarem na torcida por mim, entenderem por muitas vezes minha ausência e pela amizade de tantos anos. À Profª. Drª. Marisa Dolhnikoff pelos ensinamentos e por toda ajuda neste projeto, desde a idealização até a discussão dos resultados.

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Lung tissue remodeling in the acute respiratory distress syndrome

Cited by 4 publications

References 37 publications

Second harmonic generation microscopy reveals altered collagen microstructure in usual interstitial pneumonia versus healthy lung

Second harmonic generation microscopy reveals altered collagen microstructure in usual interstitial pneumonia versus healthy lung

Astrocytes Downregulate Inflammation in Lipopolysaccharide-Induced Acute Respiratory Distress Syndrome: Applicability to COVID-19

Efeito da exposição ao material particulado atmosférico no desenvolvimento da lesão pulmonar aguda (LPA) induzida por LPS

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