Extracellular mitochondria contribute to acute lung injury via disrupting macrophages after traumatic brain injury

Acute lung injury (ALI) is the most frequently developed complication in patients with severe traumatic brain injury (TBI), but its underlying mechanism remains poorly understood. Here, we report results from a study designed to investigate the mechanistic link between TBI and ALI in mouse models, in vitro experiments, and a patient study, specifically focusing on the role of extracellular mitochondria (exMt). We detected high levels of exMt in the alveolar lavage fluid of patients with TBI. The bronchoalveolar lavage fluid (BALF) of mice subjected to controlled cerebral cortical impact contained 4.2 ± 1.4 × 10<sup>4</sup>/µl of exMt. We further showed that non-injured mice infused with exMt intravenously developed pulmonary edema, perivascular accumulation of macrophages, inflammation, and dysfunction. Results from complementary in vitro experiments showed that exMt bound to and were phagocytosed by interstitial macrophages, resulting in autophagic flux reduction and activation of macrophages. The phagocytosis of exMt depended on the CD36 and dynamin mediated pathway, and activation of macrophages depended on exMt-derived reactive oxygen species. This study discovered a novel mechanism by which exMt contribute to the pathogenesis of TBI-induced ALI through macrophages, which are activated, develop dysfunctional autophagy, and become inflammatory after phagocytosis of exMt.

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Publication Details

Journal
Journal of Neuroinflammation
Published
2025-03-04
DOI
https://doi.org/10.1186/s12974-025-03390-x
Citations
6
Primary Topic
Traumatic Brain Injury and Neurovascular Disturbances
Type
article
Field-Weighted Citation Impact
8.34

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article

Extracellular mitochondria contribute to acute lung injury via disrupting macrophages after traumatic brain injury

Fanjian Li, Chaonan Zhang, Yafan Liu, Jing‐fei Dong et al.
6 citations
Journal of Neuroinflammation
Traumatic Brain Injury and Neurovascular Disturbances
8.34
article

Extracellular mitochondria contribute to acute lung injury via disrupting macrophages after traumatic brain injury

Fanjian Li, Chaonan Zhang, Yafan Liu, Jing‐fei Dong, Jianning Zhang, Yichi Zhang, Ying Fu, Tianrui Ma, Ying Li, Yang Li, Zilong Zhao, Zijian Zhou, Hui Guo, Hejun Zhang, Guili Yang, Kaifeng Pang, Lujia Tang
article en
6 citations

Abstract

Acute lung injury (ALI) is the most frequently developed complication in patients with severe traumatic brain injury (TBI), but its underlying mechanism remains poorly understood. Here, we report results from a study designed to investigate the mechanistic link between TBI and ALI in mouse models, in vitro experiments, and a patient study, specifically focusing on the role of extracellular mitochondria (exMt). We detected high levels of exMt in the alveolar lavage fluid of patients with TBI. The bronchoalveolar lavage fluid (BALF) of mice subjected to controlled cerebral cortical impact contained 4.2 ± 1.4 × 10<sup>4</sup>/µl of exMt. We further showed that non-injured mice infused with exMt intravenously developed pulmonary edema, perivascular accumulation of macrophages, inflammation, and dysfunction. Results from complementary in vitro experiments showed that exMt bound to and were phagocytosed by interstitial macrophages, resulting in autophagic flux reduction and activation of macrophages. The phagocytosis of exMt depended on the CD36 and dynamin mediated pathway, and activation of macrophages depended on exMt-derived reactive oxygen species. This study discovered a novel mechanism by which exMt contribute to the pathogenesis of TBI-induced ALI through macrophages, which are activated, develop dysfunctional autophagy, and become inflammatory after phagocytosis of exMt.

Journal of NeuroinflammationVol. 22(1)
Fujian Medical University (CN), Capital Medical University (CN), University of Washington (US), Bloodworks Northwest (US), Tianjin Medical University General Hospital (CN), First Affiliated Hospital of Jiangxi Medical College (CN), Beijing Institute of Neurosurgery (CN), First Affiliated Hospital of Fujian Medical University (CN), Tianjin Chest Hospital (CN), First Hospital of Qinhuangdao (CN), Pingjin Hospital (CN)
National Natural Science Foundation of China, Natural Science Foundation of Tianjin City
Good health and well-being
Openalex Percentile: Top 3%
Traumatic Brain Injury and Neurovascular Disturbances
8.34
DOIOpen Access PDFOpenAlex
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