Bernhard Fe Reiter, Natalie Bordag, Diana Schnoegl, Martina Delbeck, Tobias Madl, Hansjörg Habisch, Grazyna Kwapiszewska, Jörg Meding, Leigh M Marsh
{"title":"丙烯醛-脂多糖慢性阻塞性肺病频繁加重小鼠模型。","authors":"Bernhard Fe Reiter, Natalie Bordag, Diana Schnoegl, Martina Delbeck, Tobias Madl, Hansjörg Habisch, Grazyna Kwapiszewska, Jörg Meding, Leigh M Marsh","doi":"10.1165/rcmb.2024-0507MA","DOIUrl":null,"url":null,"abstract":"<p><p>Chronic obstructive pulmonary disease (COPD) is a severe progressive lung disease, often caused by prolonged exposure to cigarette smoke and environmental factors. Pre-clinical COPD research predominately relies on chronic smoke or elastase animal models, each with their own advantages and limitations, such as limited pathophysiological insights or long treatment times. Here we describe a novel and time efficient mouse model of COPD based on bacterial lipopolysaccharide (LPS) and the reactive aldehyde acrolein (Acro). Mice were treated once per week for four weeks with a combination of both LPS and Acro. Histological, inflammatory, and metabolomic alterations were analysed by histological quantification, multicolour flow cytometry, and nuclear magnetic resonance (NMR). Acro/LPS treatment induced moderate airspace enlargement and bronchial remodelling. These structural changes were associated with a distinct inflammatory profile marked by an increase in macrophages, and T-helper cells, as well as increased cytokines, including CXCL11, IL-17a, and TNF-α. Strong inflammation, consisting of T-helper and B-cells was detected in the perivascular and peribronchial space, and increased macrophages in the alveolar regions. Additionally, intervention with the steroid dexamethasone induced a strong reduction in T-cells and macrophages and partially ameliorated histological alterations. Furthermore, we could detect alterations in the metabolome of serum and tissue, including an increase in COPD associated metabolites like trimethylamine N-oxide, as well as a misbalance in energy related metabolites and several amino acids. In summary, we can describe a practical, representative, and time efficient mouse model of COPD, with the potential to study the immunological and pathophysiological development of the disease.</p>","PeriodicalId":7655,"journal":{"name":"American Journal of Respiratory Cell and Molecular Biology","volume":" ","pages":""},"PeriodicalIF":5.9000,"publicationDate":"2025-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"The Acrolein - Lipopolysaccharide Mouse Model for Frequent Exacerbations in COPD.\",\"authors\":\"Bernhard Fe Reiter, Natalie Bordag, Diana Schnoegl, Martina Delbeck, Tobias Madl, Hansjörg Habisch, Grazyna Kwapiszewska, Jörg Meding, Leigh M Marsh\",\"doi\":\"10.1165/rcmb.2024-0507MA\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>Chronic obstructive pulmonary disease (COPD) is a severe progressive lung disease, often caused by prolonged exposure to cigarette smoke and environmental factors. Pre-clinical COPD research predominately relies on chronic smoke or elastase animal models, each with their own advantages and limitations, such as limited pathophysiological insights or long treatment times. Here we describe a novel and time efficient mouse model of COPD based on bacterial lipopolysaccharide (LPS) and the reactive aldehyde acrolein (Acro). Mice were treated once per week for four weeks with a combination of both LPS and Acro. Histological, inflammatory, and metabolomic alterations were analysed by histological quantification, multicolour flow cytometry, and nuclear magnetic resonance (NMR). Acro/LPS treatment induced moderate airspace enlargement and bronchial remodelling. These structural changes were associated with a distinct inflammatory profile marked by an increase in macrophages, and T-helper cells, as well as increased cytokines, including CXCL11, IL-17a, and TNF-α. Strong inflammation, consisting of T-helper and B-cells was detected in the perivascular and peribronchial space, and increased macrophages in the alveolar regions. Additionally, intervention with the steroid dexamethasone induced a strong reduction in T-cells and macrophages and partially ameliorated histological alterations. Furthermore, we could detect alterations in the metabolome of serum and tissue, including an increase in COPD associated metabolites like trimethylamine N-oxide, as well as a misbalance in energy related metabolites and several amino acids. In summary, we can describe a practical, representative, and time efficient mouse model of COPD, with the potential to study the immunological and pathophysiological development of the disease.</p>\",\"PeriodicalId\":7655,\"journal\":{\"name\":\"American Journal of Respiratory Cell and Molecular Biology\",\"volume\":\" \",\"pages\":\"\"},\"PeriodicalIF\":5.9000,\"publicationDate\":\"2025-05-09\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"American Journal of Respiratory Cell and Molecular Biology\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1165/rcmb.2024-0507MA\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"BIOCHEMISTRY & MOLECULAR BIOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"American Journal of Respiratory Cell and Molecular Biology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1165/rcmb.2024-0507MA","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"BIOCHEMISTRY & MOLECULAR BIOLOGY","Score":null,"Total":0}
The Acrolein - Lipopolysaccharide Mouse Model for Frequent Exacerbations in COPD.
Chronic obstructive pulmonary disease (COPD) is a severe progressive lung disease, often caused by prolonged exposure to cigarette smoke and environmental factors. Pre-clinical COPD research predominately relies on chronic smoke or elastase animal models, each with their own advantages and limitations, such as limited pathophysiological insights or long treatment times. Here we describe a novel and time efficient mouse model of COPD based on bacterial lipopolysaccharide (LPS) and the reactive aldehyde acrolein (Acro). Mice were treated once per week for four weeks with a combination of both LPS and Acro. Histological, inflammatory, and metabolomic alterations were analysed by histological quantification, multicolour flow cytometry, and nuclear magnetic resonance (NMR). Acro/LPS treatment induced moderate airspace enlargement and bronchial remodelling. These structural changes were associated with a distinct inflammatory profile marked by an increase in macrophages, and T-helper cells, as well as increased cytokines, including CXCL11, IL-17a, and TNF-α. Strong inflammation, consisting of T-helper and B-cells was detected in the perivascular and peribronchial space, and increased macrophages in the alveolar regions. Additionally, intervention with the steroid dexamethasone induced a strong reduction in T-cells and macrophages and partially ameliorated histological alterations. Furthermore, we could detect alterations in the metabolome of serum and tissue, including an increase in COPD associated metabolites like trimethylamine N-oxide, as well as a misbalance in energy related metabolites and several amino acids. In summary, we can describe a practical, representative, and time efficient mouse model of COPD, with the potential to study the immunological and pathophysiological development of the disease.
期刊介绍:
The American Journal of Respiratory Cell and Molecular Biology publishes papers that report significant and original observations in the area of pulmonary biology. The focus of the Journal includes, but is not limited to, cellular, biochemical, molecular, developmental, genetic, and immunologic studies of lung cells and molecules.