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

Autor: Tiemei Li, Xiaotao Su, Pinglan Lu, Xinmei Kang, Mengyan Hu, Chunyi Li, Shisi Wang, Danli Lu, Shishi Shen, Huipeng Huang, Yuxin Liu, Xiaohui Deng, Wei Cai, Lei Wei, Zhengqi Lu
Jazyk: angličtina
Rok vydání: 2023
Předmět:
Zdroj: Advanced Science, Vol 10, Iss 22, Pp n/a-n/a (2023)
Druh dokumentu: article
ISSN: 2198-3844
DOI: 10.1002/advs.202206432
Popis: Abstract 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.
Databáze: Directory of Open Access Journals
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