Airway allergy causes alveolar macrophage death, profound alveolar disorganization and surfactant dysfunction

Respiratory disorders caused by allergy have been associated to bronchiolar inflammation leading to life-threatening airway narrowing. However, whether airway allergy causes alveolar dysfunction contributing to the pathology of allergic asthma remains unaddressed. To explore whether airway allergy c...

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Autores: Feo-Lucas, Lidia, Godio, Cristina, Minguito de la Escalera, María, Álvarez Ladrón, Natalia, Villarrubia, Laura H., Vega-Pérez, Adrián, González-Cintado, Leticia, Domínguez-Andrés, Jorge, García-Fojeda, Belén, Montero-Fernández, Carlos, Casals, Cristina, Autilio, Chiara, Perez-Gil, J., Crainiciuc, Georgiana, Hidalgo, Andrés, López-Bravo, María
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2023
País:España
Institución:Consejo Superior de Investigaciones Científicas (CSIC)
Repositorio:DIGITAL.CSIC. Repositorio Institucional del CSIC
OAI Identifier:oai:digital.csic.es:10261/362150
Acceso en línea:http://hdl.handle.net/10261/362150
https://api.elsevier.com/content/abstract/scopus_id/85159961552
Access Level:acceso abierto
Palabra clave:airway allergy inflammation
allergic asthma
alveolar dysfunction
alveolar macrophages (AM)
monocytes
pneumocyte hypertrophy
surfactant dysfunction
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network_acronym_str ES
network_name_str España
repository_id_str
dc.title.none.fl_str_mv Airway allergy causes alveolar macrophage death, profound alveolar disorganization and surfactant dysfunction
title Airway allergy causes alveolar macrophage death, profound alveolar disorganization and surfactant dysfunction
spellingShingle Airway allergy causes alveolar macrophage death, profound alveolar disorganization and surfactant dysfunction
Feo-Lucas, Lidia
airway allergy inflammation
allergic asthma
alveolar dysfunction
alveolar macrophages (AM)
monocytes
pneumocyte hypertrophy
surfactant dysfunction
title_short Airway allergy causes alveolar macrophage death, profound alveolar disorganization and surfactant dysfunction
title_full Airway allergy causes alveolar macrophage death, profound alveolar disorganization and surfactant dysfunction
title_fullStr Airway allergy causes alveolar macrophage death, profound alveolar disorganization and surfactant dysfunction
title_full_unstemmed Airway allergy causes alveolar macrophage death, profound alveolar disorganization and surfactant dysfunction
title_sort Airway allergy causes alveolar macrophage death, profound alveolar disorganization and surfactant dysfunction
dc.creator.none.fl_str_mv Feo-Lucas, Lidia
Godio, Cristina
Minguito de la Escalera, María
Álvarez Ladrón, Natalia
Villarrubia, Laura H.
Vega-Pérez, Adrián
González-Cintado, Leticia
Domínguez-Andrés, Jorge
García-Fojeda, Belén
Montero-Fernández, Carlos
Casals, Cristina
Autilio, Chiara
Perez-Gil, J.
Crainiciuc, Georgiana
Hidalgo, Andrés
López-Bravo, María
author Feo-Lucas, Lidia
author_facet Feo-Lucas, Lidia
Godio, Cristina
Minguito de la Escalera, María
Álvarez Ladrón, Natalia
Villarrubia, Laura H.
Vega-Pérez, Adrián
González-Cintado, Leticia
Domínguez-Andrés, Jorge
García-Fojeda, Belén
Montero-Fernández, Carlos
Casals, Cristina
Autilio, Chiara
Perez-Gil, J.
Crainiciuc, Georgiana
Hidalgo, Andrés
López-Bravo, María
author_role author
author2 Godio, Cristina
Minguito de la Escalera, María
Álvarez Ladrón, Natalia
Villarrubia, Laura H.
Vega-Pérez, Adrián
González-Cintado, Leticia
Domínguez-Andrés, Jorge
García-Fojeda, Belén
Montero-Fernández, Carlos
Casals, Cristina
Autilio, Chiara
Perez-Gil, J.
Crainiciuc, Georgiana
Hidalgo, Andrés
López-Bravo, María
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Ministerio de Economía y Competitividad (España)
Ministerio de Ciencia e Innovación (España)
Comunidad de Madrid
Consejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]
dc.subject.none.fl_str_mv airway allergy inflammation
allergic asthma
alveolar dysfunction
alveolar macrophages (AM)
monocytes
pneumocyte hypertrophy
surfactant dysfunction
topic airway allergy inflammation
allergic asthma
alveolar dysfunction
alveolar macrophages (AM)
monocytes
pneumocyte hypertrophy
surfactant dysfunction
description Respiratory disorders caused by allergy have been associated to bronchiolar inflammation leading to life-threatening airway narrowing. However, whether airway allergy causes alveolar dysfunction contributing to the pathology of allergic asthma remains unaddressed. To explore whether airway allergy causes alveolar dysfunction that might contribute to the pathology of allergic asthma, alveolar structural and functional alterations were analyzed during house dust mite (HDM)-induced airway allergy in mice, by flow cytometry, light and electron microscopy, monocyte transfer experiments, assessment of intra-alveolarly-located cells, analysis of alveolar macrophage regeneration in Cx3cr1 cre:R26-yfp chimeras, analysis of surfactant-associated proteins, and study of lung surfactant biophysical properties by captive bubble surfactometry. Our results demonstrate that HDM-induced airway allergic reactions caused severe alveolar dysfunction, leading to alveolar macrophage death, pneumocyte hypertrophy and surfactant dysfunction. SP-B/C proteins were reduced in allergic lung surfactant, that displayed a reduced efficiency to form surface-active films, increasing the risk of atelectasis. Original alveolar macrophages were replaced by monocyte-derived alveolar macrophages, that persisted at least two months after the resolution of allergy. Monocyte to alveolar macrophage transition occurred through an intermediate stage of pre-alveolar macrophage and was paralleled with translocation into the alveolar space, Siglec-F upregulation, and downregulation of CX3CR1. These data support that the severe respiratory disorders caused by asthmatic reactions not only result from bronchiolar inflammation, but additionally from alveolar dysfunction compromising an efficient gas exchange.
publishDate 2023
dc.date.none.fl_str_mv 2023
2024
2024
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dc.identifier.none.fl_str_mv http://hdl.handle.net/10261/362150
https://api.elsevier.com/content/abstract/scopus_id/85159961552
url http://hdl.handle.net/10261/362150
https://api.elsevier.com/content/abstract/scopus_id/85159961552
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Frontiers in immunology
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https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2023.1125984/full

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dc.publisher.none.fl_str_mv Frontiers Media
publisher.none.fl_str_mv Frontiers Media
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spelling Airway allergy causes alveolar macrophage death, profound alveolar disorganization and surfactant dysfunctionFeo-Lucas, LidiaGodio, CristinaMinguito de la Escalera, MaríaÁlvarez Ladrón, NataliaVillarrubia, Laura H.Vega-Pérez, AdriánGonzález-Cintado, LeticiaDomínguez-Andrés, JorgeGarcía-Fojeda, BelénMontero-Fernández, CarlosCasals, CristinaAutilio, ChiaraPerez-Gil, J.Crainiciuc, GeorgianaHidalgo, AndrésLópez-Bravo, Maríaairway allergy inflammationallergic asthmaalveolar dysfunctionalveolar macrophages (AM)monocytespneumocyte hypertrophysurfactant dysfunctionRespiratory disorders caused by allergy have been associated to bronchiolar inflammation leading to life-threatening airway narrowing. However, whether airway allergy causes alveolar dysfunction contributing to the pathology of allergic asthma remains unaddressed. To explore whether airway allergy causes alveolar dysfunction that might contribute to the pathology of allergic asthma, alveolar structural and functional alterations were analyzed during house dust mite (HDM)-induced airway allergy in mice, by flow cytometry, light and electron microscopy, monocyte transfer experiments, assessment of intra-alveolarly-located cells, analysis of alveolar macrophage regeneration in Cx3cr1 cre:R26-yfp chimeras, analysis of surfactant-associated proteins, and study of lung surfactant biophysical properties by captive bubble surfactometry. Our results demonstrate that HDM-induced airway allergic reactions caused severe alveolar dysfunction, leading to alveolar macrophage death, pneumocyte hypertrophy and surfactant dysfunction. SP-B/C proteins were reduced in allergic lung surfactant, that displayed a reduced efficiency to form surface-active films, increasing the risk of atelectasis. Original alveolar macrophages were replaced by monocyte-derived alveolar macrophages, that persisted at least two months after the resolution of allergy. Monocyte to alveolar macrophage transition occurred through an intermediate stage of pre-alveolar macrophage and was paralleled with translocation into the alveolar space, Siglec-F upregulation, and downregulation of CX3CR1. These data support that the severe respiratory disorders caused by asthmatic reactions not only result from bronchiolar inflammation, but additionally from alveolar dysfunction compromising an efficient gas exchange.This work was supported by the Ministerio de Economía y Competitividad (Grant SAF2015-69905 to CaA and Grant SAF2015-65307-R to CC), Ministerio de Ciencia e Innovación (Grants PGC2018-101899-B-100 and PID2021-122748OB-I00 to CaA, Grants RTI2018-094355‐B‐I00 and PID2021-123044OB-I00 to CC and Grant PID2021-124932OB-I00 to JP-G), and Comunidad de Madrid (Grant P2018/NMT4389 to JP-G).Peer reviewedFrontiers MediaMinisterio de Economía y Competitividad (España)Ministerio de Ciencia e Innovación (España)Comunidad de MadridConsejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]202420242023info:eu-repo/semantics/articlehttp://purl.org/coar/resource_type/c_6501Publisher's versioninfo:eu-repo/semantics/publishedVersionhttp://hdl.handle.net/10261/362150https://api.elsevier.com/content/abstract/scopus_id/85159961552reponame:DIGITAL.CSIC. Repositorio Institucional del CSICinstname:Consejo Superior de Investigaciones Científicas (CSIC)Inglés#PLACEHOLDER_PARENT_METADATA_VALUE##PLACEHOLDER_PARENT_METADATA_VALUE##PLACEHOLDER_PARENT_METADATA_VALUE##PLACEHOLDER_PARENT_METADATA_VALUE##PLACEHOLDER_PARENT_METADATA_VALUE##PLACEHOLDER_PARENT_METADATA_VALUE##PLACEHOLDER_PARENT_METADATA_VALUE#info:eu-repo/grantAgreement/MINECO//SAF2015-65307-Rinfo:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2017-2020/PGC2018-101899-B-I00info:eu-repo/grantAgreement/MINECO//SAF2015-69905-Pinfo:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2021-2023/PID2021-122748OB-I00info:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2017-2020/RTI2018-094355-B-I00info:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2021-2023/PID2021-123044OB-I00info:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2021-2023/PID2021-124932OB-I00Frontiers in immunologyapplication/pdfhttps://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2023.1125984/fullSíinfo:eu-repo/semantics/openAccessoai:digital.csic.es:10261/3621502026-05-22T06:33:51Z
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