Modulation of alveolar macrophage and mitochondrial fitness by medicinal plant-derived nanovesicles to mitigate acute lung injury and viral pneumonia

• Published in: Journal of nanobiotechnology Vol. 22; no. 1; p. 190
• Main Authors: Ye, Lusha, Gao, Yanan, Mok, Simon Wing Fai, Liao, Wucan, Wang, Yazhou, Chen, Changjiang, Yang, Lijun, Zhang, Junfeng, Shi, Liyun
• Format: Journal Article
• Language: English
• Published: England BioMed Central Ltd 18.04.2024; BioMed Central; BMC
• Subjects: Acute lung injury; Acute Lung Injury - pathology; Acute respiratory distress syndrome; Alveolar macrophages; Analysis; Animals; Artemisia-derived nanovesicles; Bacterial pneumonia; Care and treatment; Diagnosis; GABA; Gamma-aminobutyric acid; gamma-Aminobutyric Acid - metabolism; Genes; Health aspects; Inflammation; Lung - metabolism; Macrophages; Macrophages, Alveolar - metabolism; Medicinal plants; Medicine, Botanic; Medicine, Herbal; Mice; Mitochondria; Mitochondria - pathology; Mitochondrial function; Plants, Medicinal; Pneumonia; Pneumonia - metabolism; Pneumonia, Viral - drug therapy; China; Acute lung injury; Gamma-aminobutyric acid; Artemisia-derived nanovesicles; Mitochondrial function; Alveolar macrophages
• ISSN: 1477-3155; 1477-3155
• DOI: 10.1186/s12951-024-02473-w

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.