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

Autor:	Feo-Lucas L; Departamento de Inmunología y Oncología, Centro Nacional de Biotecnología/ Consejo Superior de Investigaciones Científicas (CSIC), Madrid, Spain., Godio C; Departamento de Inmunología y Oncología, Centro Nacional de Biotecnología/ Consejo Superior de Investigaciones Científicas (CSIC), Madrid, Spain., Minguito de la Escalera M; Departamento de Inmunología y Oncología, Centro Nacional de Biotecnología/ Consejo Superior de Investigaciones Científicas (CSIC), Madrid, Spain., Alvarez-Ladrón N; Departamento de Inmunología y Oncología, Centro Nacional de Biotecnología/ Consejo Superior de Investigaciones Científicas (CSIC), Madrid, Spain., Villarrubia LH; Departamento de Inmunología y Oncología, Centro Nacional de Biotecnología/ Consejo Superior de Investigaciones Científicas (CSIC), Madrid, Spain., Vega-Pérez A; Departamento de Inmunología y Oncología, Centro Nacional de Biotecnología/ Consejo Superior de Investigaciones Científicas (CSIC), Madrid, Spain., González-Cintado L; Departamento de Inmunología y Oncología, Centro Nacional de Biotecnología/ Consejo Superior de Investigaciones Científicas (CSIC), Madrid, Spain., Domínguez-Andrés J; Departamento de Inmunología y Oncología, Centro Nacional de Biotecnología/ Consejo Superior de Investigaciones Científicas (CSIC), Madrid, Spain., García-Fojeda B; Departamento de Bioquímica y Biología Molecular, Facultad de Biología, Universidad Complutense, Madrid, Spain., Montero-Fernández C; Departamento de Bioquímica y Biología Molecular, Facultad de Biología, Universidad Complutense, Madrid, Spain., Casals C; Departamento de Bioquímica y Biología Molecular, Facultad de Biología, Universidad Complutense, Madrid, Spain., Autilio C; Departamento de Bioquímica y Biología Molecular, Facultad de Biología, Universidad Complutense, Madrid, Spain.; Instituto de Investigación Sanitaria Hospital 12 de Octubre i+12, Madrid, Spain., Pérez-Gil J; Departamento de Bioquímica y Biología Molecular, Facultad de Biología, Universidad Complutense, Madrid, Spain.; Instituto de Investigación Sanitaria Hospital 12 de Octubre i+12, Madrid, Spain., Crainiciuc G; Centro Nacional de Investigaciones Cardiovaculares Carlos III, Madrid, Spain., Hidalgo A; Centro Nacional de Investigaciones Cardiovaculares Carlos III, Madrid, Spain., López-Bravo M; Departamento de Inmunología y Oncología, Centro Nacional de Biotecnología/ Consejo Superior de Investigaciones Científicas (CSIC), Madrid, Spain., Ardavín C; Departamento de Inmunología y Oncología, Centro Nacional de Biotecnología/ Consejo Superior de Investigaciones Científicas (CSIC), Madrid, Spain.
Jazyk:	angličtina
Zdroj:	Frontiers in immunology [Front Immunol] 2023 May 10; Vol. 14, pp. 1125984. Date of Electronic Publication: 2023 May 10 (Print Publication: 2023).
DOI:	10.3389/fimmu.2023.1125984
Abstrakt:	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. Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (Copyright © 2023 Feo-Lucas, Godio, Minguito de la Escalera, Alvarez-Ladrón, Villarrubia, Vega-Pérez, González-Cintado, Domínguez-Andrés, García-Fojeda, Montero-Fernández, Casals, Autilio, Pérez-Gil, Crainiciuc, Hidalgo, López-Bravo and Ardavín.)
Databáze:	MEDLINE
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