Extracellular Vesicles From Bone Marrow-Derived Macrophages Enriched in ARG1 Enhance Microglial Phagocytosis and Haematoma Clearance Following Intracerebral Haemorrhage

被引:0
|
作者
Hu, Libin [1 ,2 ,3 ]
Chen, Zihang [1 ,2 ,3 ]
Lu, Jianglong [4 ]
Jiang, Shandong [1 ,2 ]
Lin, Haopu [1 ,2 ]
Zhou, Jiayin [1 ,2 ]
Wang, Ning [4 ]
Ding, Chao [4 ]
Ni, Weifang [4 ]
Peng, Haitao [4 ]
Li, Yin [1 ,2 ]
He, Xuchao [1 ,2 ]
Li, Jianru [1 ,2 ]
Jing, Chaohui [5 ]
Cao, Yang [6 ]
Zhou, Hang [1 ,2 ,3 ]
Yan, Feng [1 ,2 ,3 ]
Chen, Gao [1 ,2 ,3 ]
机构
[1] Zhejiang Univ, Affiliated Hosp 2, Sch Med, Dept Neurosurg, Hangzhou, Peoples R China
[2] Zhejiang Key Lab Res & Transformat Major Neurosurg, Hangzhou, Peoples R China
[3] State Key Lab Transvasc Implantat Devices, Hangzhou, Peoples R China
[4] Zhejiang Univ, Sch Med, Hangzhou, Zhejiang, Peoples R China
[5] Shanghai Jiao Tong Univ, XinHua Hosp, Dept Neurosurg, Sch Med, Shanghai, Peoples R China
[6] Westlake Univ, Affiliated Hangzhou Peoples Hosp 1, Sch Med, Dept Neurosurg, Hangzhou, Peoples R China
基金
中国国家自然科学基金;
关键词
ARG1; BMDM; EVs; ICH; microglia; phagocytosis; EXOSOMES; RECEPTOR; ERYTHROPHAGOCYTOSIS; EFFEROCYTOSIS; ACTIVATION; RESOLUTION; DISEASE; TOOLS; CELLS; GAMMA;
D O I
10.1002/jev2.70041
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
Microglial phagocytosis of haematomas is crucial for neural functional recovery following intracerebral haemorrhage (ICH), a process regulated by various factors from within and outside the central nervous system (CNS). Extracellular vesicles (EVs), significant mediators of intercellular communication, have been demonstrated to play a pivotal role in the pathogenesis and progression of CNS diseases. However, the regulatory role of endogenous EVs on the phagocytic capacity of microglia post-ICH remains elusive. Utilising multi-omics analysis of brain tissue-derived EVs proteomics and single-cell RNA sequencing, this study identified that bone marrow-derived macrophages (BMDMs) potentially enhance microglial phagocytosis via EVs following ICH. By blocking BMDMs and reducing ARG1 in BMDM-derived EVs, we demonstrated that BMDMs facilitate erythrophagocytosis by delivering ARG1 to microglia via EVs post-ICH. EVs-carried ARG1 was found to augment phagocytosis by promoting RAC1-dependent cytoskeletal remodelling in microglia. Collectively, this research uncovers an intercellular communication pathway from BMDMs to microglia mediated by EVs post-ICH. This provides a novel paradigm for EV-mediated intercellular communication mechanisms and suggests a promising therapeutic potential for BMDM-derived EVs in the treatment of ICH.
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页数:24
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