Modulation of alveolar macrophage and mitochondrial fitness by medicinal plant-derived nanovesicles to mitigate acute lung injury and viral pneumonia
Abstract Acute lung injury (ALI) is generally caused by severe respiratory infection and characterized by overexuberant inflammatory responses and inefficient pathogens-containing, the two major processes wherein alveolar macrophages (AMs) play a central role. Dysfunctional mitochondria have been li...
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| Format: | Article |
| Language: | English |
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BMC
2024-04-01
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| Series: | Journal of Nanobiotechnology |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12951-024-02473-w |
| _version_ | 1827276962909913088 |
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| author | Lusha Ye Yanan Gao Simon Wing Fai Mok Wucan Liao Yazhou Wang Changjiang Chen Lijun Yang Junfeng Zhang Liyun Shi |
| author_facet | Lusha Ye Yanan Gao Simon Wing Fai Mok Wucan Liao Yazhou Wang Changjiang Chen Lijun Yang Junfeng Zhang Liyun Shi |
| author_sort | Lusha Ye |
| collection | DOAJ |
| description | Abstract Acute lung injury (ALI) is generally caused by severe respiratory infection and characterized by overexuberant inflammatory responses and inefficient pathogens-containing, the two major processes wherein alveolar macrophages (AMs) play a central role. Dysfunctional mitochondria have been linked with distorted macrophages and hence lung disorders, but few treatments are currently available to correct these defects. Plant-derive nanovesicles have gained significant attention because of their therapeutic potential, but the targeting cells and the underlying mechanism remain elusive. We herein prepared the nanovesicles from Artemisia annua, a well-known medicinal plant with multiple attributes involving anti-inflammatory, anti-infection, and metabolism-regulating properties. By applying three mice models of acute lung injury caused by bacterial endotoxin, influenza A virus (IAV) and SARS-CoV-2 pseudovirus respectively, we showed that Artemisia-derived nanovesicles (ADNVs) substantially alleviated lung immunopathology and raised the survival rate of challenged mice. Macrophage depletion and adoptive transfer studies confirmed the requirement of AMs for ADNVs effects. We identified that gamma-aminobutyric acid (GABA) enclosed in the vesicles is a major molecular effector mediating the regulatory roles of ADNVs. Specifically, GABA acts on macrophages through GABA receptors, promoting mitochondrial gene programming and bioenergy generation, reducing oxidative stress and inflammatory signals, thereby enhancing the adaptability of AMs to inflammation resolution. Collectively, this study identifies a promising nanotherapeutics for alleviating lung pathology, and elucidates a mechanism whereby the canonical neurotransmitter modifies AMs and mitochondria to resume tissue homeostasis, which may have broader implications for treating critical pulmonary diseases such as COVID-19. |
| first_indexed | 2024-04-24T07:11:47Z |
| format | Article |
| id | doaj.art-50c887b161164c778bd6fa4334ebcecf |
| institution | Directory Open Access Journal |
| issn | 1477-3155 |
| language | English |
| last_indexed | 2024-04-24T07:11:47Z |
| publishDate | 2024-04-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Nanobiotechnology |
| spelling | doaj.art-50c887b161164c778bd6fa4334ebcecf2024-04-21T11:29:11ZengBMCJournal of Nanobiotechnology1477-31552024-04-0122112010.1186/s12951-024-02473-wModulation of alveolar macrophage and mitochondrial fitness by medicinal plant-derived nanovesicles to mitigate acute lung injury and viral pneumoniaLusha Ye0Yanan Gao1Simon Wing Fai Mok2Wucan Liao3Yazhou Wang4Changjiang Chen5Lijun Yang6Junfeng Zhang7Liyun Shi8Institute of Translational Medicine, Zhejiang Shuren UniversityDepartment of Immunology and Medical Microbiology, Nanjing University of Chinese MedicineDepartment of Medicine, Macau University of Science and TechnologyDepartment of Immunology and Medical Microbiology, Nanjing University of Chinese MedicineDepartment of Immunology and Medical Microbiology, Nanjing University of Chinese MedicineDepartment of Immunology and Medical Microbiology, Nanjing University of Chinese MedicineInstitute of Translational Medicine, Zhejiang Shuren UniversityDepartment of Immunology and Medical Microbiology, Nanjing University of Chinese MedicineInstitute of Translational Medicine, Zhejiang Shuren UniversityAbstract Acute lung injury (ALI) is generally caused by severe respiratory infection and characterized by overexuberant inflammatory responses and inefficient pathogens-containing, the two major processes wherein alveolar macrophages (AMs) play a central role. Dysfunctional mitochondria have been linked with distorted macrophages and hence lung disorders, but few treatments are currently available to correct these defects. Plant-derive nanovesicles have gained significant attention because of their therapeutic potential, but the targeting cells and the underlying mechanism remain elusive. We herein prepared the nanovesicles from Artemisia annua, a well-known medicinal plant with multiple attributes involving anti-inflammatory, anti-infection, and metabolism-regulating properties. By applying three mice models of acute lung injury caused by bacterial endotoxin, influenza A virus (IAV) and SARS-CoV-2 pseudovirus respectively, we showed that Artemisia-derived nanovesicles (ADNVs) substantially alleviated lung immunopathology and raised the survival rate of challenged mice. Macrophage depletion and adoptive transfer studies confirmed the requirement of AMs for ADNVs effects. We identified that gamma-aminobutyric acid (GABA) enclosed in the vesicles is a major molecular effector mediating the regulatory roles of ADNVs. Specifically, GABA acts on macrophages through GABA receptors, promoting mitochondrial gene programming and bioenergy generation, reducing oxidative stress and inflammatory signals, thereby enhancing the adaptability of AMs to inflammation resolution. Collectively, this study identifies a promising nanotherapeutics for alleviating lung pathology, and elucidates a mechanism whereby the canonical neurotransmitter modifies AMs and mitochondria to resume tissue homeostasis, which may have broader implications for treating critical pulmonary diseases such as COVID-19.https://doi.org/10.1186/s12951-024-02473-wArtemisia-derived nanovesiclesAlveolar macrophagesAcute lung injuryGamma-aminobutyric acidMitochondrial function |
| spellingShingle | Lusha Ye Yanan Gao Simon Wing Fai Mok Wucan Liao Yazhou Wang Changjiang Chen Lijun Yang Junfeng Zhang Liyun Shi Modulation of alveolar macrophage and mitochondrial fitness by medicinal plant-derived nanovesicles to mitigate acute lung injury and viral pneumonia Journal of Nanobiotechnology Artemisia-derived nanovesicles Alveolar macrophages Acute lung injury Gamma-aminobutyric acid Mitochondrial function |
| title | Modulation of alveolar macrophage and mitochondrial fitness by medicinal plant-derived nanovesicles to mitigate acute lung injury and viral pneumonia |
| title_full | Modulation of alveolar macrophage and mitochondrial fitness by medicinal plant-derived nanovesicles to mitigate acute lung injury and viral pneumonia |
| title_fullStr | Modulation of alveolar macrophage and mitochondrial fitness by medicinal plant-derived nanovesicles to mitigate acute lung injury and viral pneumonia |
| title_full_unstemmed | Modulation of alveolar macrophage and mitochondrial fitness by medicinal plant-derived nanovesicles to mitigate acute lung injury and viral pneumonia |
| title_short | Modulation of alveolar macrophage and mitochondrial fitness by medicinal plant-derived nanovesicles to mitigate acute lung injury and viral pneumonia |
| title_sort | modulation of alveolar macrophage and mitochondrial fitness by medicinal plant derived nanovesicles to mitigate acute lung injury and viral pneumonia |
| topic | Artemisia-derived nanovesicles Alveolar macrophages Acute lung injury Gamma-aminobutyric acid Mitochondrial function |
| url | https://doi.org/10.1186/s12951-024-02473-w |
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