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Correlation between Neutrophil Extracellular Traps (NETs) Expression and Primary Graft Dysfunction Following Human Lung Transplantation

Primary graft dysfunction (PGD) is characterized by alveolar epithelial and vascular endothelial damage and inflammation, lung edema and hypoxemia. Up to one-third of recipients develop the most severe form of PGD (Grade 3; PGD3). Animal studies suggest that neutrophils contribute to the inflammator...

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Autores principales: Bonneau, Steven, Landry, Caroline, Bégin, Stéphanie, Adam, Damien, Villeneuve, Louis, Clavet-Lanthier, Marie-Élaine, Dasilva, Ariane, Charles, Elcha, Dumont, Benjamin L., Neagoe, Paul-Eduard, Brochiero, Emmanuelle, Menaouar, Ahmed, Nasir, Basil, Stevens, Louis-Mathieu, Ferraro, Pasquale, Noiseux, Nicolas, Sirois, Martin G.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9656095/
https://www.ncbi.nlm.nih.gov/pubmed/36359815
http://dx.doi.org/10.3390/cells11213420
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author Bonneau, Steven
Landry, Caroline
Bégin, Stéphanie
Adam, Damien
Villeneuve, Louis
Clavet-Lanthier, Marie-Élaine
Dasilva, Ariane
Charles, Elcha
Dumont, Benjamin L.
Neagoe, Paul-Eduard
Brochiero, Emmanuelle
Menaouar, Ahmed
Nasir, Basil
Stevens, Louis-Mathieu
Ferraro, Pasquale
Noiseux, Nicolas
Sirois, Martin G.
author_facet Bonneau, Steven
Landry, Caroline
Bégin, Stéphanie
Adam, Damien
Villeneuve, Louis
Clavet-Lanthier, Marie-Élaine
Dasilva, Ariane
Charles, Elcha
Dumont, Benjamin L.
Neagoe, Paul-Eduard
Brochiero, Emmanuelle
Menaouar, Ahmed
Nasir, Basil
Stevens, Louis-Mathieu
Ferraro, Pasquale
Noiseux, Nicolas
Sirois, Martin G.
author_sort Bonneau, Steven
collection PubMed
description Primary graft dysfunction (PGD) is characterized by alveolar epithelial and vascular endothelial damage and inflammation, lung edema and hypoxemia. Up to one-third of recipients develop the most severe form of PGD (Grade 3; PGD3). Animal studies suggest that neutrophils contribute to the inflammatory process through neutrophil extracellular traps (NETs) release (NETosis). NETs are composed of DNA filaments decorated with granular proteins contributing to vascular occlusion associated with PGD. The main objective was to correlate NETosis in PGD3 (n = 9) versus non-PGD3 (n = 27) recipients in an exploratory study. Clinical data and blood samples were collected from donors and recipients pre-, intra- and postoperatively (up to 72 h). Inflammatory inducers of NETs’ release (IL-8, IL-6 and C-reactive protein [CRP]) and components (myeloperoxidase [MPO], MPO-DNA complexes and cell-free DNA [cfDNA]) were quantified by ELISA. When available, histology, immunohistochemistry and immunofluorescence techniques were performed on lung biopsies from donor grafts collected during the surgery to evaluate the presence of activated neutrophils and NETs. Lung biopsies from donor grafts collected during transplantation presented various degrees of vascular occlusion including neutrophils undergoing NETosis. Additionally, in recipients intra- and postoperatively, circulating inflammatory (IL-6, IL-8) and NETosis biomarkers (MPO-DNA, MPO, cfDNA) were up to 4-fold higher in PGD3 recipients compared to non-PGD3 (p = 0.041 to 0.001). In summary, perioperative elevation of NETosis biomarkers is associated with PGD3 following human lung transplantation and these biomarkers might serve to identify recipients at risk of PGD3 and initiate preventive therapies.
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spelling pubmed-96560952022-11-15 Correlation between Neutrophil Extracellular Traps (NETs) Expression and Primary Graft Dysfunction Following Human Lung Transplantation Bonneau, Steven Landry, Caroline Bégin, Stéphanie Adam, Damien Villeneuve, Louis Clavet-Lanthier, Marie-Élaine Dasilva, Ariane Charles, Elcha Dumont, Benjamin L. Neagoe, Paul-Eduard Brochiero, Emmanuelle Menaouar, Ahmed Nasir, Basil Stevens, Louis-Mathieu Ferraro, Pasquale Noiseux, Nicolas Sirois, Martin G. Cells Article Primary graft dysfunction (PGD) is characterized by alveolar epithelial and vascular endothelial damage and inflammation, lung edema and hypoxemia. Up to one-third of recipients develop the most severe form of PGD (Grade 3; PGD3). Animal studies suggest that neutrophils contribute to the inflammatory process through neutrophil extracellular traps (NETs) release (NETosis). NETs are composed of DNA filaments decorated with granular proteins contributing to vascular occlusion associated with PGD. The main objective was to correlate NETosis in PGD3 (n = 9) versus non-PGD3 (n = 27) recipients in an exploratory study. Clinical data and blood samples were collected from donors and recipients pre-, intra- and postoperatively (up to 72 h). Inflammatory inducers of NETs’ release (IL-8, IL-6 and C-reactive protein [CRP]) and components (myeloperoxidase [MPO], MPO-DNA complexes and cell-free DNA [cfDNA]) were quantified by ELISA. When available, histology, immunohistochemistry and immunofluorescence techniques were performed on lung biopsies from donor grafts collected during the surgery to evaluate the presence of activated neutrophils and NETs. Lung biopsies from donor grafts collected during transplantation presented various degrees of vascular occlusion including neutrophils undergoing NETosis. Additionally, in recipients intra- and postoperatively, circulating inflammatory (IL-6, IL-8) and NETosis biomarkers (MPO-DNA, MPO, cfDNA) were up to 4-fold higher in PGD3 recipients compared to non-PGD3 (p = 0.041 to 0.001). In summary, perioperative elevation of NETosis biomarkers is associated with PGD3 following human lung transplantation and these biomarkers might serve to identify recipients at risk of PGD3 and initiate preventive therapies. MDPI 2022-10-29 /pmc/articles/PMC9656095/ /pubmed/36359815 http://dx.doi.org/10.3390/cells11213420 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Bonneau, Steven
Landry, Caroline
Bégin, Stéphanie
Adam, Damien
Villeneuve, Louis
Clavet-Lanthier, Marie-Élaine
Dasilva, Ariane
Charles, Elcha
Dumont, Benjamin L.
Neagoe, Paul-Eduard
Brochiero, Emmanuelle
Menaouar, Ahmed
Nasir, Basil
Stevens, Louis-Mathieu
Ferraro, Pasquale
Noiseux, Nicolas
Sirois, Martin G.
Correlation between Neutrophil Extracellular Traps (NETs) Expression and Primary Graft Dysfunction Following Human Lung Transplantation
title Correlation between Neutrophil Extracellular Traps (NETs) Expression and Primary Graft Dysfunction Following Human Lung Transplantation
title_full Correlation between Neutrophil Extracellular Traps (NETs) Expression and Primary Graft Dysfunction Following Human Lung Transplantation
title_fullStr Correlation between Neutrophil Extracellular Traps (NETs) Expression and Primary Graft Dysfunction Following Human Lung Transplantation
title_full_unstemmed Correlation between Neutrophil Extracellular Traps (NETs) Expression and Primary Graft Dysfunction Following Human Lung Transplantation
title_short Correlation between Neutrophil Extracellular Traps (NETs) Expression and Primary Graft Dysfunction Following Human Lung Transplantation
title_sort correlation between neutrophil extracellular traps (nets) expression and primary graft dysfunction following human lung transplantation
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9656095/
https://www.ncbi.nlm.nih.gov/pubmed/36359815
http://dx.doi.org/10.3390/cells11213420
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