炎症性内皮细胞表达S1PR1抑制剂CD69以诱导血管泄漏
Michel V Levesque1, Andreane Cartier1, Yueh-Chien Lin1
1Vascular Biology Program, Boston Children's Hospital, Department of Surgery, Harvard Medical School, Boston, Massachusetts, USA.
The Journal of biological chemistry
|July 5, 2025
概括
炎症会在内皮细胞中触发CD69,该细胞将神素1-酸盐受体-1 (S1PR1) 内化,增加血管泄漏. 在小鼠中阻断CD69可以减少病毒感染期间的泄漏.
科学领域:
- 内皮细胞生物学 内皮细胞生物学
- 免疫学 免疫学 免疫学
- 血管生理学 血管生理学
背景情况:
- 内皮屏障功能障碍导致炎症和组织损伤.
- 氨酸1-酸盐受体-1 (S1PR1) 对于内皮结的完整性和屏障功能至关重要.
- 像TNFα和TLR激动剂这样的细胞因子可以激活内皮细胞.
研究的目的:
- 为了研究CD69在炎症和病毒感染期间内皮细胞中的作用.
- 阐明CD69影响内皮屏障功能和S1PR1信号传递的机制.
- 为了确定CD69是否在体内有助于血管泄漏.
主要方法:
- 用TNFα和多氨基/多细胞 (pI:C) 激活内皮细胞 (ECs).
- 通过NFκB途径诱导CD69的分析.
- 评估S1PR1内细胞分裂,信号和屏障功能.
- 在体内研究使用病毒感染 (H1N1,MHV-A59) 和腺相关病毒介导的基因传递在小鼠.
- 遗传小鼠模型缺乏内皮细胞CD69.
主要成果:
- 由TNFα和pI:C激活的EC通过NFκB通路诱导CD69.
- 内皮CD69促进S1PR1内细胞分裂,抑制下游信号和屏障功能.
- 病毒感染 (H1N1,MHV-A59) 和TLR激动剂在肺部EC中诱导CD69.
- 肺EC中CD69的过度表达降低了S1PR1和Claudin-5,增加了血管透性.
- 缺乏内皮CD69的小鼠在H1N1感染期间表现出减少的肺血管泄漏.
结论:
- 在炎症和病毒防御过程中内皮细胞的激活会诱导CD69,从而降低S1PR1的调节,从而导致血管泄漏.
- CD69对抗EC中保护性S1PR1通路,可能加剧炎症.
- 向CD69可能提供一种治疗策略,以减轻炎症状况和感染中的血管泄漏.
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