Nebulized Heparin Attenuates Pulmonary Coagulopathy and Inflammation through Alveolar Macrophages in a Rat Model of Acute Lung Injury

Objective Alveolar macrophages play a key role in the development and resolution of acute respiratory distress syndrome (ARDS), modulating the inflammatory response and the coagulation cascade in lungs. Anti-coagulants may be helpful in the treatment of ARDS. This study investigated the effects of n...

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Autores: Chimenti, Laura|||0000-0002-3109-7779, Camprubí-Rimblas, Marta|||0000-0002-4085-5324, Guillamat-Prats, Raquel|||0000-0001-6960-0985, Gómez, Maria Nieves, Tijero, Jessica, Blanch, Lluís|||0000-0002-4158-7464, Artigas Raventós, Antoni|||0000-0002-8029-1017
Tipo de recurso: artículo
Fecha de publicación:2017
País:España
Institución:Universitat Autònoma de Barcelona
Repositorio:Dipòsit Digital de Documents de la UAB
Idioma:inglés
OAI Identifier:oai:ddd.uab.cat:201726
Acceso en línea:https://ddd.uab.cat/record/201726
https://dx.doi.org/urn:doi:10.1160/TH17-05-0347
Access Level:acceso abierto
Palabra clave:Acute respiratory distress syndrome
Acute lung injury
Anti-coagulants
Heparin
Alveolar macrophages
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spelling Nebulized Heparin Attenuates Pulmonary Coagulopathy and Inflammation through Alveolar Macrophages in a Rat Model of Acute Lung InjuryChimenti, Laura|||0000-0002-3109-7779Camprubí-Rimblas, Marta|||0000-0002-4085-5324Guillamat-Prats, Raquel|||0000-0001-6960-0985Gómez, Maria NievesTijero, JessicaBlanch, Lluís|||0000-0002-4158-7464Artigas Raventós, Antoni|||0000-0002-8029-1017Acute respiratory distress syndromeAcute lung injuryAnti-coagulantsHeparinAlveolar macrophagesObjective Alveolar macrophages play a key role in the development and resolution of acute respiratory distress syndrome (ARDS), modulating the inflammatory response and the coagulation cascade in lungs. Anti-coagulants may be helpful in the treatment of ARDS. This study investigated the effects of nebulized heparin on the role of alveolar macrophages in limiting lung coagulation and inflammatory response in an animal model of acute lung injury (ALI). Methods Rats were randomized to four experimental groups. In three groups, ALI was induced by intratracheal instillation of lipopolysaccharide (LPS) and heparin was nebulized at constant oxygen flow: the LPS/Hep group received nebulized heparin 4 and 8 hours after injury; the Hep/LPS/Hep group received nebulized heparin 30 minutes before and 4 and 8 hours after LPS-induced injury; the LPS/Sal group received nebulized saline 4 and 8 hours after injury. The control group received only saline. Animals were exsanguinated 24 hours after LPS instillation. Lung tissue, bronchoalveolar lavage fluid (BALF) and alveolar macrophages isolated from BALF were analysed. Results LPS increased protein concentration, oedema and neutrophils in BALF as well as procoagulant and proinflammatory mediators in lung tissue and alveolar macrophages. In lung tissue, nebulized heparin attenuated ALI through decreasing procoagulant (tissue factor, thrombin-anti-thrombin complexes, fibrin degradation products) and proinflammatory (interleukin 6, tumour necrosis factor alpha) pathways. In alveolar macrophages, nebulized heparin reduced expression of procoagulant genes and the effectors of transforming growth factor beta (Smad 2, Smad 3) and nuclear factor kappa B (p-selectin, CCL-2). Pre-treatment resulted in more pronounced attenuation. Conclusion Nebulized heparin reduced pulmonary coagulopathy and inflammation without producing systemic bleeding, partly by modulating alveolar macrophages. 22017-01-0120172017-01-01Articlehttp://purl.org/coar/resource_type/c_6501VoRhttp://purl.org/coar/version/c_970fb48d4fbd8a85info:eu-repo/semantics/articleapplication/pdfhttps://ddd.uab.cat/record/201726https://dx.doi.org/urn:doi:10.1160/TH17-05-0347reponame:Dipòsit Digital de Documents de la UABinstname:Universitat Autònoma de BarcelonaInglésengInstituto de Salud Carlos III https://doi.org/10.13039/501100004587 PI12-02548open accesshttp://purl.org/coar/access_right/c_abf2Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, i la comunicació pública de l'obra, sempre que no sigui amb finalitats comercials, i sempre que es reconegui l'autoria de l'obra original. No es permet la creació d'obres derivades.https://creativecommons.org/licenses/by-nc-nd/4.0/info:eu-repo/semantics/openAccessoai:ddd.uab.cat:2017262026-06-06T12:50:31Z
dc.title.none.fl_str_mv Nebulized Heparin Attenuates Pulmonary Coagulopathy and Inflammation through Alveolar Macrophages in a Rat Model of Acute Lung Injury
title Nebulized Heparin Attenuates Pulmonary Coagulopathy and Inflammation through Alveolar Macrophages in a Rat Model of Acute Lung Injury
spellingShingle Nebulized Heparin Attenuates Pulmonary Coagulopathy and Inflammation through Alveolar Macrophages in a Rat Model of Acute Lung Injury
Chimenti, Laura|||0000-0002-3109-7779
Acute respiratory distress syndrome
Acute lung injury
Anti-coagulants
Heparin
Alveolar macrophages
title_short Nebulized Heparin Attenuates Pulmonary Coagulopathy and Inflammation through Alveolar Macrophages in a Rat Model of Acute Lung Injury
title_full Nebulized Heparin Attenuates Pulmonary Coagulopathy and Inflammation through Alveolar Macrophages in a Rat Model of Acute Lung Injury
title_fullStr Nebulized Heparin Attenuates Pulmonary Coagulopathy and Inflammation through Alveolar Macrophages in a Rat Model of Acute Lung Injury
title_full_unstemmed Nebulized Heparin Attenuates Pulmonary Coagulopathy and Inflammation through Alveolar Macrophages in a Rat Model of Acute Lung Injury
title_sort Nebulized Heparin Attenuates Pulmonary Coagulopathy and Inflammation through Alveolar Macrophages in a Rat Model of Acute Lung Injury
dc.creator.none.fl_str_mv Chimenti, Laura|||0000-0002-3109-7779
Camprubí-Rimblas, Marta|||0000-0002-4085-5324
Guillamat-Prats, Raquel|||0000-0001-6960-0985
Gómez, Maria Nieves
Tijero, Jessica
Blanch, Lluís|||0000-0002-4158-7464
Artigas Raventós, Antoni|||0000-0002-8029-1017
author Chimenti, Laura|||0000-0002-3109-7779
author_facet Chimenti, Laura|||0000-0002-3109-7779
Camprubí-Rimblas, Marta|||0000-0002-4085-5324
Guillamat-Prats, Raquel|||0000-0001-6960-0985
Gómez, Maria Nieves
Tijero, Jessica
Blanch, Lluís|||0000-0002-4158-7464
Artigas Raventós, Antoni|||0000-0002-8029-1017
author_role author
author2 Camprubí-Rimblas, Marta|||0000-0002-4085-5324
Guillamat-Prats, Raquel|||0000-0001-6960-0985
Gómez, Maria Nieves
Tijero, Jessica
Blanch, Lluís|||0000-0002-4158-7464
Artigas Raventós, Antoni|||0000-0002-8029-1017
author2_role author
author
author
author
author
author
dc.subject.none.fl_str_mv Acute respiratory distress syndrome
Acute lung injury
Anti-coagulants
Heparin
Alveolar macrophages
topic Acute respiratory distress syndrome
Acute lung injury
Anti-coagulants
Heparin
Alveolar macrophages
description Objective Alveolar macrophages play a key role in the development and resolution of acute respiratory distress syndrome (ARDS), modulating the inflammatory response and the coagulation cascade in lungs. Anti-coagulants may be helpful in the treatment of ARDS. This study investigated the effects of nebulized heparin on the role of alveolar macrophages in limiting lung coagulation and inflammatory response in an animal model of acute lung injury (ALI). Methods Rats were randomized to four experimental groups. In three groups, ALI was induced by intratracheal instillation of lipopolysaccharide (LPS) and heparin was nebulized at constant oxygen flow: the LPS/Hep group received nebulized heparin 4 and 8 hours after injury; the Hep/LPS/Hep group received nebulized heparin 30 minutes before and 4 and 8 hours after LPS-induced injury; the LPS/Sal group received nebulized saline 4 and 8 hours after injury. The control group received only saline. Animals were exsanguinated 24 hours after LPS instillation. Lung tissue, bronchoalveolar lavage fluid (BALF) and alveolar macrophages isolated from BALF were analysed. Results LPS increased protein concentration, oedema and neutrophils in BALF as well as procoagulant and proinflammatory mediators in lung tissue and alveolar macrophages. In lung tissue, nebulized heparin attenuated ALI through decreasing procoagulant (tissue factor, thrombin-anti-thrombin complexes, fibrin degradation products) and proinflammatory (interleukin 6, tumour necrosis factor alpha) pathways. In alveolar macrophages, nebulized heparin reduced expression of procoagulant genes and the effectors of transforming growth factor beta (Smad 2, Smad 3) and nuclear factor kappa B (p-selectin, CCL-2). Pre-treatment resulted in more pronounced attenuation. Conclusion Nebulized heparin reduced pulmonary coagulopathy and inflammation without producing systemic bleeding, partly by modulating alveolar macrophages.
publishDate 2017
dc.date.none.fl_str_mv 2
2017-01-01
2017
2017-01-01
dc.type.none.fl_str_mv Article
http://purl.org/coar/resource_type/c_6501
VoR
http://purl.org/coar/version/c_970fb48d4fbd8a85
dc.type.openaire.fl_str_mv info:eu-repo/semantics/article
format article
dc.identifier.none.fl_str_mv https://ddd.uab.cat/record/201726
https://dx.doi.org/urn:doi:10.1160/TH17-05-0347
url https://ddd.uab.cat/record/201726
https://dx.doi.org/urn:doi:10.1160/TH17-05-0347
dc.language.none.fl_str_mv Inglés
eng
language_invalid_str_mv Inglés
language eng
dc.relation.none.fl_str_mv Instituto de Salud Carlos III https://doi.org/10.13039/501100004587 PI12-02548
dc.rights.none.fl_str_mv open access
http://purl.org/coar/access_right/c_abf2
https://creativecommons.org/licenses/by-nc-nd/4.0/
dc.rights.openaire.fl_str_mv info:eu-repo/semantics/openAccess
rights_invalid_str_mv open access
http://purl.org/coar/access_right/c_abf2
https://creativecommons.org/licenses/by-nc-nd/4.0/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.source.none.fl_str_mv reponame:Dipòsit Digital de Documents de la UAB
instname:Universitat Autònoma de Barcelona
instname_str Universitat Autònoma de Barcelona
reponame_str Dipòsit Digital de Documents de la UAB
collection Dipòsit Digital de Documents de la UAB
repository.name.fl_str_mv
repository.mail.fl_str_mv
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