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Elastase- and LPS-Exposed Cpa3(Cre/+) and ST2(-/-) Mice Develop Unimpaired Obstructive Pulmonary Disease
IL-33 and its receptor ST2, as well as mast cells and their mediators, have been implicated in the development of chronic obstructive pulmonary disease (COPD). However, whether mast cells and the ST2 receptor play a critical role in COPD pathophysiology remains unclear. Here, we performed repeated i...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Frontiers Media S.A.
2022
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9043106/ https://www.ncbi.nlm.nih.gov/pubmed/35493481 http://dx.doi.org/10.3389/fimmu.2022.830859 |
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author | Cardenas, Eduardo I. Alvarado-Vazquez, Perla A. Mendez-Enriquez, Erika Danielsson, Erik A. Hallgren, Jenny |
author_facet | Cardenas, Eduardo I. Alvarado-Vazquez, Perla A. Mendez-Enriquez, Erika Danielsson, Erik A. Hallgren, Jenny |
author_sort | Cardenas, Eduardo I. |
collection | PubMed |
description | IL-33 and its receptor ST2, as well as mast cells and their mediators, have been implicated in the development of chronic obstructive pulmonary disease (COPD). However, whether mast cells and the ST2 receptor play a critical role in COPD pathophysiology remains unclear. Here, we performed repeated intranasal administrations of porcine pancreatic elastase and LPS for four weeks to study COPD-like disease in wildtype, ST2-deficient, and Cpa3(Cre/+) mice, which lack mast cells and have a partial reduction in basophils. Alveolar enlargement and changes in spirometry-like parameters, e.g. increased dynamic compliance and decreased expiratory capacity, were evident one day after the final LPS challenge and worsened over time. The elastase/LPS model also induced mild COPD-like airway inflammation, which encompassed a transient increase in lung mast cell progenitors, but not in mature mast cells. While ST2-deficient and Cpa3(Cre/+) mice developed reduced pulmonary function uninterruptedly, they had a defective inflammatory response. Importantly, both ST2-deficient and Cpa3(Cre/+) mice had fewer alveolar macrophages, known effector cells in COPD. Elastase/LPS instillation in vivo also caused increased bronchiole contraction in precision cut lung slices challenged with methacholine ex vivo, which occurred in a mast cell-independent fashion. Taken together, our data suggest that the ST2 receptor and mast cells play a minor role in COPD pathophysiology by sustaining alveolar macrophages. |
format | Online Article Text |
id | pubmed-9043106 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-90431062022-04-28 Elastase- and LPS-Exposed Cpa3(Cre/+) and ST2(-/-) Mice Develop Unimpaired Obstructive Pulmonary Disease Cardenas, Eduardo I. Alvarado-Vazquez, Perla A. Mendez-Enriquez, Erika Danielsson, Erik A. Hallgren, Jenny Front Immunol Immunology IL-33 and its receptor ST2, as well as mast cells and their mediators, have been implicated in the development of chronic obstructive pulmonary disease (COPD). However, whether mast cells and the ST2 receptor play a critical role in COPD pathophysiology remains unclear. Here, we performed repeated intranasal administrations of porcine pancreatic elastase and LPS for four weeks to study COPD-like disease in wildtype, ST2-deficient, and Cpa3(Cre/+) mice, which lack mast cells and have a partial reduction in basophils. Alveolar enlargement and changes in spirometry-like parameters, e.g. increased dynamic compliance and decreased expiratory capacity, were evident one day after the final LPS challenge and worsened over time. The elastase/LPS model also induced mild COPD-like airway inflammation, which encompassed a transient increase in lung mast cell progenitors, but not in mature mast cells. While ST2-deficient and Cpa3(Cre/+) mice developed reduced pulmonary function uninterruptedly, they had a defective inflammatory response. Importantly, both ST2-deficient and Cpa3(Cre/+) mice had fewer alveolar macrophages, known effector cells in COPD. Elastase/LPS instillation in vivo also caused increased bronchiole contraction in precision cut lung slices challenged with methacholine ex vivo, which occurred in a mast cell-independent fashion. Taken together, our data suggest that the ST2 receptor and mast cells play a minor role in COPD pathophysiology by sustaining alveolar macrophages. Frontiers Media S.A. 2022-04-13 /pmc/articles/PMC9043106/ /pubmed/35493481 http://dx.doi.org/10.3389/fimmu.2022.830859 Text en Copyright © 2022 Cardenas, Alvarado-Vazquez, Mendez-Enriquez, Danielsson and Hallgren https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Immunology Cardenas, Eduardo I. Alvarado-Vazquez, Perla A. Mendez-Enriquez, Erika Danielsson, Erik A. Hallgren, Jenny Elastase- and LPS-Exposed Cpa3(Cre/+) and ST2(-/-) Mice Develop Unimpaired Obstructive Pulmonary Disease |
title | Elastase- and LPS-Exposed Cpa3(Cre/+) and ST2(-/-) Mice Develop Unimpaired Obstructive Pulmonary Disease |
title_full | Elastase- and LPS-Exposed Cpa3(Cre/+) and ST2(-/-) Mice Develop Unimpaired Obstructive Pulmonary Disease |
title_fullStr | Elastase- and LPS-Exposed Cpa3(Cre/+) and ST2(-/-) Mice Develop Unimpaired Obstructive Pulmonary Disease |
title_full_unstemmed | Elastase- and LPS-Exposed Cpa3(Cre/+) and ST2(-/-) Mice Develop Unimpaired Obstructive Pulmonary Disease |
title_short | Elastase- and LPS-Exposed Cpa3(Cre/+) and ST2(-/-) Mice Develop Unimpaired Obstructive Pulmonary Disease |
title_sort | elastase- and lps-exposed cpa3(cre/+) and st2(-/-) mice develop unimpaired obstructive pulmonary disease |
topic | Immunology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9043106/ https://www.ncbi.nlm.nih.gov/pubmed/35493481 http://dx.doi.org/10.3389/fimmu.2022.830859 |
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