衰老的内皮细胞在炎症组织中促进了致病性中性粒细胞的贩运
Loïc Rolas1, Monja Stein1, Anna Barkaway1
1Centre for Microvascular Research, William Harvey Research Institute, Faculty of Medicine and Dentistry, Queen Mary University of London, London, UK.
EMBO reports
|June 25, 2024
概括
衰老的内皮细胞 (ECs) 通过增加中性粒细胞粘附和微血管泄漏来促进炎症. 阻止EC CXCL1通路可以抑制这些促炎反应,提供治疗点.
科学领域:
- 血管生物学 血管生物学
- 免疫学 免疫学 免疫学
- 衰老研究研究 衰老研究
背景情况:
- 细胞衰老,特别是内皮细胞 (ECs),与血管功能障碍和炎症有关.
- 衰老ECs在调节单细胞水平的体内炎症细胞相互作用中的确切作用仍然不太清楚.
研究的目的:
- 在体内调查内皮细胞 (EC) 衰老对中性粒细胞-静脉壁相互作用的影响.
- 阐明衰老ECs导致炎症的潜在分子机制.
主要方法:
- 在表现EC衰老的EC特异性progeroid小鼠模型中使用了高分辨率的共聚焦内显微镜.
- 在炎症组织上进行了转录和免疫光分析.
- 检查了老化的人类ECs在体外的促炎作用.
主要成果:
- 陈旧的ECs,表达素,促进长时间的中性粒细胞粘附和爬行以细胞自主的方式.
- 衰老的ECs调解了中性粒细胞依赖的微血管泄漏.
- 在衰老的EC上观察到高ECCXCL1水平,并且阻断CXCL1减弱了失调的中性粒细胞反应.
- 培养的老年人ECs显示中性粒细胞的附着和激活增加.
结论:
- 衰老的内皮细胞通过调节中性粒细胞的行为来积极驱动过度炎症.
- EC CXCL1通路是老化ECs引发的炎症的关键调解者.
- 这些发现为单细胞水平的EC衰老驱动的炎症提供了新的机制性见解.
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