Bone Marrow Mesenchymal Stem Cell-Derived Dermcidin-Containing Migrasomes enhance LC3-Associated Phagocytosis of Pulmonary Macrophages and Protect against Post-Stroke Pneumonia

被引：34

作者：

Li, Tiemei ^{[1
,2
]}

Su, Xiaotao ^{[1
]}

Lu, Pinglan ^{[3
]}

Kang, Xinmei ^{[1
]}

Hu, Mengyan ^{[1
,4
]}

Li, Chunyi ^{[1
]}

Wang, Shisi ^{[1
]}

Lu, Danli ^{[1
]}

Shen, Shishi ^{[1
]}

Huang, Huipeng ^{[1
]}

Liu, Yuxin ^{[1
]}

Deng, Xiaohui ^{[1
]}

Cai, Wei ^{[1
,2
,3
]}

Wei, Lei ^{[1
]}

Lu, Zhengqi ^{[1
]}

机构：

[1] Sun Yat Sen Univ, Affiliated Hosp 3, Mental & Neurol Dis Res Ctr, Dept Neurol, Guangzhou 510630, Peoples R China

[2] Sun Yat Sen Univ, Affiliated Hosp 3, Ctr Clin Immunol, Mental & Neurol Dis Res Ctr, Guangzhou 510630, Peoples R China

[3] Sun Yat Sen Univ, Zhongshan Sch Med, Guangdong Prov Key Lab Brain Funct & Dis, Guangzhou 510630, Peoples R China

[4] Sun Yat Sen Univ, Affiliated Hosp 3, Surg Intens Care Unit, Guangzhou 510630, Peoples R China

来源：

ADVANCED SCIENCE | 2023年 / 10卷 / 22期

基金：

中国国家自然科学基金;

关键词：

bone marrow mesenchymal stem cell; macrophage; migrasome; post-stroke pneumonia; EXTRACELLULAR VESICLES; ISCHEMIC-STROKE; STROMAL CELLS; BRAIN-INJURY; NEUROINFLAMMATION; ANTIBIOTICS; IMPROVES;

D O I：

10.1002/advs.202206432

中图分类号：

O6 [化学];

学科分类号：

0703 ;

摘要：

Pneumonia is one of the leading causes of death in patients with acute ischemic stroke (AIS). Antibiotics fail to improve prognosis of patients with post-stroke pneumonia, albeit suppressing infection, due to adverse impacts on the immune system. The current study reports that bone marrow mesenchymal stem cells (BM-MSC) downregulate bacterial load in the lungs of stroke mice models. RNA-sequencing of the lung from BM-MSC-treated stroke models indicates that BM-MSC modulates pulmonary macrophage activities after cerebral ischemia. Mechanistically, BM-MSC promotes the bacterial phagocytosis of pulmonary macrophages through releasing migrasomes, which are migration-dependent extracellular vesicles. With liquid chromatography-tandem mass spectrometry (LC-MS/MS), the result shows that BM-MSC are found to load the antibacterial peptide dermcidin (DCD) in migrasomes upon bacterial stimulation. Besides the antibiotic effect, DCD enhances LC3-associated phagocytosis (LAP) of macrophages, facilitating their bacterial clearance. The data demonstrate that BM-MSC is a promising therapeutic candidate against post-stroke pneumonia, with dual functions of anti-infection and immunol modulation, which is more than a match for antibiotics treatment.

引用

页数：17