Apoptosis inhibitor of macrophage (AIM)/CD5L is involved in the pathogenesis of COPD
Abstract Background Alveolar macrophages (AMs) and AM-produced matrix metalloprotease (MMP)-12 are known to play critical roles in the pathogenesis of chronic obstructive pulmonary disease (COPD). The apoptosis inhibitor of the macrophages (AIM)/CD5 molecule-like (CD5L) is a multifunctional protein...
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| Format: | Article |
| Language: | English |
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BMC
2023-08-01
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| Series: | Respiratory Research |
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| Online Access: | https://doi.org/10.1186/s12931-023-02508-0 |
| _version_ | 1797556997808193536 |
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| author | Michiko Takimoto-Sato Masaru Suzuki Hiroki Kimura Haiyan Ge Munehiro Matsumoto Hironi Makita Satoko Arai Toru Miyazaki Masaharu Nishimura Satoshi Konno |
| author_facet | Michiko Takimoto-Sato Masaru Suzuki Hiroki Kimura Haiyan Ge Munehiro Matsumoto Hironi Makita Satoko Arai Toru Miyazaki Masaharu Nishimura Satoshi Konno |
| author_sort | Michiko Takimoto-Sato |
| collection | DOAJ |
| description | Abstract Background Alveolar macrophages (AMs) and AM-produced matrix metalloprotease (MMP)-12 are known to play critical roles in the pathogenesis of chronic obstructive pulmonary disease (COPD). The apoptosis inhibitor of the macrophages (AIM)/CD5 molecule-like (CD5L) is a multifunctional protein secreted by the macrophages that mainly exists in the blood in a combined form with the immunoglobulin (Ig)M pentamer. Although AIM has both facilitative and suppressive roles in various diseases, its role in COPD remains unclear. Methods We investigated the role of AIM in COPD pathogenesis using porcine pancreas elastase (PPE)-induced and cigarette smoke-induced emphysema mouse models and an in vitro model using AMs. We also analyzed the differences in the blood AIM/IgM ratio among nonsmokers, healthy smokers, and patients with COPD and investigated the association between the blood AIM/IgM ratio and COPD exacerbations and mortality in patients with COPD. Results Emphysema formation, inflammation, and cell death in the lungs were attenuated in AIM−/− mice compared with wild-type (WT) mice in both PPE- and cigarette smoke-induced emphysema models. The PPE-induced increase in MMP-12 was attenuated in AIM−/− mice at both the mRNA and protein levels. According to in vitro experiments using AMs stimulated with cigarette smoke extract, the MMP-12 level was decreased in AIM−/− mice compared with WT mice. This decrease was reversed by the addition of recombinant AIM. Furthermore, an analysis of clinical samples showed that patients with COPD had a higher blood AIM/IgM ratio than healthy smokers. Additionally, the blood AIM/IgM ratio was positively associated with disease severity in patients with COPD. A higher AIM/IgM ratio was also associated with a shorter time to the first COPD exacerbation and higher all-cause and respiratory mortality. Conclusions AIM facilitates the development of COPD by upregulating MMP-12. Additionally, a higher blood AIM/IgM ratio was associated with poor prognosis in patients with COPD. Trial Registration This clinical study, which included nonsmokers, healthy smokers, and smokers with COPD, was approved by the Ethics Committee of the Hokkaido University Hospital (012–0075, date of registration: September 5, 2012). The Hokkaido COPD cohort study was approved by the Ethics Committee of the Hokkaido University School of Medicine (med02-001, date of registration: December 25, 2002). |
| first_indexed | 2024-03-10T17:10:04Z |
| format | Article |
| id | doaj.art-5ec91e8278204269a4f5a920e4566207 |
| institution | Directory Open Access Journal |
| issn | 1465-993X |
| language | English |
| last_indexed | 2024-03-10T17:10:04Z |
| publishDate | 2023-08-01 |
| publisher | BMC |
| record_format | Article |
| series | Respiratory Research |
| spelling | doaj.art-5ec91e8278204269a4f5a920e45662072023-11-20T10:40:33ZengBMCRespiratory Research1465-993X2023-08-0124111310.1186/s12931-023-02508-0Apoptosis inhibitor of macrophage (AIM)/CD5L is involved in the pathogenesis of COPDMichiko Takimoto-Sato0Masaru Suzuki1Hiroki Kimura2Haiyan Ge3Munehiro Matsumoto4Hironi Makita5Satoko Arai6Toru Miyazaki7Masaharu Nishimura8Satoshi Konno9Department of Respiratory Medicine, Faculty of Medicine, Graduate School of Medicine, Hokkaido UniversityDepartment of Respiratory Medicine, Faculty of Medicine, Graduate School of Medicine, Hokkaido UniversityDepartment of Respiratory Medicine, Faculty of Medicine, Graduate School of Medicine, Hokkaido UniversityDepartment of Respiratory and Critical Care Medicine, Huadong Hospital, Fudan UniversityDepartment of Respiratory Medicine, Faculty of Medicine, Graduate School of Medicine, Hokkaido UniversityHokkaido Medical Research Institute of Respiratory DiseasesLaboratory of Molecular Biomedicine for Pathogenesis, Center for Disease Biology and Integrative Medicine, Faculty of Medicine, University of TokyoThe Institute for AIM MedicineDepartment of Respiratory Medicine, Faculty of Medicine, Graduate School of Medicine, Hokkaido UniversityDepartment of Respiratory Medicine, Faculty of Medicine, Graduate School of Medicine, Hokkaido UniversityAbstract Background Alveolar macrophages (AMs) and AM-produced matrix metalloprotease (MMP)-12 are known to play critical roles in the pathogenesis of chronic obstructive pulmonary disease (COPD). The apoptosis inhibitor of the macrophages (AIM)/CD5 molecule-like (CD5L) is a multifunctional protein secreted by the macrophages that mainly exists in the blood in a combined form with the immunoglobulin (Ig)M pentamer. Although AIM has both facilitative and suppressive roles in various diseases, its role in COPD remains unclear. Methods We investigated the role of AIM in COPD pathogenesis using porcine pancreas elastase (PPE)-induced and cigarette smoke-induced emphysema mouse models and an in vitro model using AMs. We also analyzed the differences in the blood AIM/IgM ratio among nonsmokers, healthy smokers, and patients with COPD and investigated the association between the blood AIM/IgM ratio and COPD exacerbations and mortality in patients with COPD. Results Emphysema formation, inflammation, and cell death in the lungs were attenuated in AIM−/− mice compared with wild-type (WT) mice in both PPE- and cigarette smoke-induced emphysema models. The PPE-induced increase in MMP-12 was attenuated in AIM−/− mice at both the mRNA and protein levels. According to in vitro experiments using AMs stimulated with cigarette smoke extract, the MMP-12 level was decreased in AIM−/− mice compared with WT mice. This decrease was reversed by the addition of recombinant AIM. Furthermore, an analysis of clinical samples showed that patients with COPD had a higher blood AIM/IgM ratio than healthy smokers. Additionally, the blood AIM/IgM ratio was positively associated with disease severity in patients with COPD. A higher AIM/IgM ratio was also associated with a shorter time to the first COPD exacerbation and higher all-cause and respiratory mortality. Conclusions AIM facilitates the development of COPD by upregulating MMP-12. Additionally, a higher blood AIM/IgM ratio was associated with poor prognosis in patients with COPD. Trial Registration This clinical study, which included nonsmokers, healthy smokers, and smokers with COPD, was approved by the Ethics Committee of the Hokkaido University Hospital (012–0075, date of registration: September 5, 2012). The Hokkaido COPD cohort study was approved by the Ethics Committee of the Hokkaido University School of Medicine (med02-001, date of registration: December 25, 2002).https://doi.org/10.1186/s12931-023-02508-0Chronic obstructive lung diseaseApoptosis inhibitor of macrophageMatrix metalloprotease-12Alveolar macrophage |
| spellingShingle | Michiko Takimoto-Sato Masaru Suzuki Hiroki Kimura Haiyan Ge Munehiro Matsumoto Hironi Makita Satoko Arai Toru Miyazaki Masaharu Nishimura Satoshi Konno Apoptosis inhibitor of macrophage (AIM)/CD5L is involved in the pathogenesis of COPD Respiratory Research Chronic obstructive lung disease Apoptosis inhibitor of macrophage Matrix metalloprotease-12 Alveolar macrophage |
| title | Apoptosis inhibitor of macrophage (AIM)/CD5L is involved in the pathogenesis of COPD |
| title_full | Apoptosis inhibitor of macrophage (AIM)/CD5L is involved in the pathogenesis of COPD |
| title_fullStr | Apoptosis inhibitor of macrophage (AIM)/CD5L is involved in the pathogenesis of COPD |
| title_full_unstemmed | Apoptosis inhibitor of macrophage (AIM)/CD5L is involved in the pathogenesis of COPD |
| title_short | Apoptosis inhibitor of macrophage (AIM)/CD5L is involved in the pathogenesis of COPD |
| title_sort | apoptosis inhibitor of macrophage aim cd5l is involved in the pathogenesis of copd |
| topic | Chronic obstructive lung disease Apoptosis inhibitor of macrophage Matrix metalloprotease-12 Alveolar macrophage |
| url | https://doi.org/10.1186/s12931-023-02508-0 |
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