Cargando…
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...
Autores principales: | , , , , , , , , , , , , , , , , |
---|---|
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 |
_version_ | 1784829348514103296 |
---|---|
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. |
format | Online Article Text |
id | pubmed-9656095 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
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 |
work_keys_str_mv | AT bonneausteven correlationbetweenneutrophilextracellulartrapsnetsexpressionandprimarygraftdysfunctionfollowinghumanlungtransplantation AT landrycaroline correlationbetweenneutrophilextracellulartrapsnetsexpressionandprimarygraftdysfunctionfollowinghumanlungtransplantation AT beginstephanie correlationbetweenneutrophilextracellulartrapsnetsexpressionandprimarygraftdysfunctionfollowinghumanlungtransplantation AT adamdamien correlationbetweenneutrophilextracellulartrapsnetsexpressionandprimarygraftdysfunctionfollowinghumanlungtransplantation AT villeneuvelouis correlationbetweenneutrophilextracellulartrapsnetsexpressionandprimarygraftdysfunctionfollowinghumanlungtransplantation AT clavetlanthiermarieelaine correlationbetweenneutrophilextracellulartrapsnetsexpressionandprimarygraftdysfunctionfollowinghumanlungtransplantation AT dasilvaariane correlationbetweenneutrophilextracellulartrapsnetsexpressionandprimarygraftdysfunctionfollowinghumanlungtransplantation AT charleselcha correlationbetweenneutrophilextracellulartrapsnetsexpressionandprimarygraftdysfunctionfollowinghumanlungtransplantation AT dumontbenjaminl correlationbetweenneutrophilextracellulartrapsnetsexpressionandprimarygraftdysfunctionfollowinghumanlungtransplantation AT neagoepauleduard correlationbetweenneutrophilextracellulartrapsnetsexpressionandprimarygraftdysfunctionfollowinghumanlungtransplantation AT brochieroemmanuelle correlationbetweenneutrophilextracellulartrapsnetsexpressionandprimarygraftdysfunctionfollowinghumanlungtransplantation AT menaouarahmed correlationbetweenneutrophilextracellulartrapsnetsexpressionandprimarygraftdysfunctionfollowinghumanlungtransplantation AT nasirbasil correlationbetweenneutrophilextracellulartrapsnetsexpressionandprimarygraftdysfunctionfollowinghumanlungtransplantation AT stevenslouismathieu correlationbetweenneutrophilextracellulartrapsnetsexpressionandprimarygraftdysfunctionfollowinghumanlungtransplantation AT ferraropasquale correlationbetweenneutrophilextracellulartrapsnetsexpressionandprimarygraftdysfunctionfollowinghumanlungtransplantation AT noiseuxnicolas correlationbetweenneutrophilextracellulartrapsnetsexpressionandprimarygraftdysfunctionfollowinghumanlungtransplantation AT siroismarting correlationbetweenneutrophilextracellulartrapsnetsexpressionandprimarygraftdysfunctionfollowinghumanlungtransplantation |