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Macrophage lineage cells-derived migrasomes activate complement-dependent blood-brain barrier damage in cerebral amyloid angiopathy mouse model

Author

Listed:
  • Mengyan Hu

    (The Third Affiliated Hospital of Sun Yat-sen University
    Guangdong Provincial Key Laboratory of Brain Function and Disease
    The Third Affiliated Hospital of Sun Yat-sen University)

  • Tiemei Li

    (The Third Affiliated Hospital of Sun Yat-sen University)

  • Xiaomeng Ma

    (The Third Affiliated Hospital of Sun Yat-sen University)

  • Sanxin Liu

    (The Third Affiliated Hospital of Sun Yat-sen University)

  • Chunyi Li

    (The Third Affiliated Hospital of Sun Yat-sen University)

  • Zhenchao Huang

    (The Third Affiliated Hospital of Sun Yat-Sen University)

  • Yinyao Lin

    (The Third Affiliated Hospital of Sun Yat-sen University)

  • Ruizhen Wu

    (The Third Affiliated Hospital of Sun Yat-sen University)

  • Shisi Wang

    (The Third Affiliated Hospital of Sun Yat-sen University)

  • Danli Lu

    (The Third Affiliated Hospital of Sun Yat-sen University)

  • Tingting Lu

    (The Third Affiliated Hospital of Sun Yat-sen University)

  • Xuejiao Men

    (The Third Affiliated Hospital of Sun Yat-sen University)

  • Shishi Shen

    (The Third Affiliated Hospital of Sun Yat-sen University)

  • Huipeng Huang

    (The Third Affiliated Hospital of Sun Yat-sen University)

  • Yuxin Liu

    (The Third Affiliated Hospital of Sun Yat-sen University)

  • Kangyu Song

    (The Third Affiliated Hospital of Sun Yat-sen University)

  • Banghao Jian

    (The Third Affiliated Hospital of Sun Yat-sen University)

  • Yuxuan Jiang

    (The Third Affiliated Hospital of Sun Yat-sen University)

  • Wei Qiu

    (The Third Affiliated Hospital of Sun Yat-sen University)

  • Quentin Liu

    (State Key Laboratory of Oncology in South China)

  • Zhengqi Lu

    (The Third Affiliated Hospital of Sun Yat-sen University)

  • Wei Cai

    (The Third Affiliated Hospital of Sun Yat-sen University
    Guangdong Provincial Key Laboratory of Brain Function and Disease
    The Third Affiliated Hospital of Sun Yat-sen University)

Abstract

Accumulation of amyloid beta protein (Aβ) in brain vessels damages blood brain barrier (BBB) integrity in cerebral amyloid angiopathy (CAA). Macrophage lineage cells scavenge Aβ and produce disease-modifying mediators. Herein, we report that Aβ40-induced macrophage-derived migrasomes are sticky to blood vessels in skin biopsy samples from CAA patients and brain tissue from CAA mouse models (Tg-SwDI/B and 5xFAD mice). We show that CD5L is packed in migrasomes and docked to blood vessels, and that enrichment of CD5L impairs the resistance to complement activation. Increased migrasome-producing capacity of macrophages and membrane attack complex (MAC) in blood are associated with disease severity in both patients and Tg-SwDI/B mice. Of note, complement inhibitory treatment protects against migrasomes-mediated blood-brain barrier injury in Tg-SwDI/B mice. We thus propose that macrophage-derived migrasomes and the consequent complement activation are potential biomarkers and therapeutic targets in CAA.

Suggested Citation

  • Mengyan Hu & Tiemei Li & Xiaomeng Ma & Sanxin Liu & Chunyi Li & Zhenchao Huang & Yinyao Lin & Ruizhen Wu & Shisi Wang & Danli Lu & Tingting Lu & Xuejiao Men & Shishi Shen & Huipeng Huang & Yuxin Liu &, 2023. "Macrophage lineage cells-derived migrasomes activate complement-dependent blood-brain barrier damage in cerebral amyloid angiopathy mouse model," Nature Communications, Nature, vol. 14(1), pages 1-19, December.
    • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-39693-x
    DOI: 10.1038/s41467-023-39693-x
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    References listed on IDEAS

    as
    1. Alexandra Grubman & Xin Yi Choo & Gabriel Chew & John F. Ouyang & Guizhi Sun & Nathan P. Croft & Fernando J. Rossello & Rebecca Simmons & Sam Buckberry & Dulce Vargas Landin & Jahnvi Pflueger & Teresa, 2021. "Transcriptional signature in microglia associated with Aβ plaque phagocytosis," Nature Communications, Nature, vol. 12(1), pages 1-22, December.
    2. Yejie Shi & Lili Zhang & Hongjian Pu & Leilei Mao & Xiaoming Hu & Xiaoyan Jiang & Na Xu & R. Anne Stetler & Feng Zhang & Xiangrong Liu & Rehana K. Leak & Richard F. Keep & Xunming Ji & Jun Chen, 2016. "Rapid endothelial cytoskeletal reorganization enables early blood–brain barrier disruption and long-term ischaemic reperfusion brain injury," Nature Communications, Nature, vol. 7(1), pages 1-18, April.
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