Macrophage lineage cells-derived migrasomes activate complement-dependent blood-brain barrier damage in cerebral amyloid angiopathy mouse model.
Mengyan HuTiemei LiXiaomeng MaSanxin LiuChunyi LiZhenchao HuangYinyao LinRuizhen WuShisi WangDanli LuTingting LuXuejiao MenShishi ShenHuipeng HuangYuxin LiuKangyu SongBanghao JianYuxuan JiangWei QiuQuentin LiuZhengqi LuSong Guo ZhengPublished in: Nature communications (2023)
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.
Keyphrases
- blood brain barrier
- cerebral ischemia
- mouse model
- end stage renal disease
- induced apoptosis
- ejection fraction
- adipose tissue
- newly diagnosed
- peritoneal dialysis
- high fat diet induced
- prognostic factors
- cell cycle arrest
- white matter
- brain injury
- multiple sclerosis
- patient reported outcomes
- endothelial cells
- cell proliferation
- signaling pathway
- soft tissue
- high glucose