TNF-α诱导VE-cadherin依赖的间隙/JAIL循环通过中性粒细胞转移所必需的中间状态
Jan Philip Kipcke1,2,3, Maria Odenthal-Schnittler1,2, Mohammed Aldirawi3
1Max-Planck-Institute for Molecular Biomedicine, Münster, Germany.
Frontiers in immunology
|September 25, 2025
概括
这项研究揭示了炎症形态表型 (IMP) 对于中性粒细胞的跨内皮移动 (TEM) 是至关重要的. 它涉及由MLC酸化调节的动态缺口形成和恢复周期,提供新的治疗点.
科学领域:
- 细胞生物学 细胞生物学
- 免疫学 免疫学 免疫学
- 身体生理学 身体生理学
背景情况:
- 内皮细胞表型控制白细胞的跨内皮细胞迁移 (TEM).
- 瘤亡因子-α (TNF-α) 诱导细胞粘附分子 (CAM) 的表达,调解白细胞相互作用.
- 炎症形态表型 (IMP) 的作用,包括TEM期间的屏障功能下降和形状变化,尚未完全理解.
研究的目的:
- 调查TNF-α诱导的IMP在中性粒细胞TEM中的作用.
- 阐明在TEM期间调节IMP和内皮屏障功能的机制.
- 根据IMP法规确定潜在的炎症性疾病治疗点.
主要方法:
- 对TNF-α诱导的内皮细胞形态和屏障功能的分析.
- 对分子事件的研究,包括MLC酸化,actin动态和VE-cadherin局部化.
- 评估中性粒细胞TEM对操纵IMP和VE-cadherin表达的反应.
主要成果:
- 由TNF-α诱导的IMP对中性粒细胞TEM至关重要,并调节内皮屏障功能.
- IMP 通过涉及过渡性障碍增强的状态进行进展,其次是形状变化和差距形成.
- 由MLC酸化驱动的GAP/JAIL (连接关联的间歇性乳类) 循环,通过创建和重新封闭细胞间隙来促进TEM.
- 过度表达VE-cadherin抑制了IMP和gap/JAIL循环,显著减少了TEM.
结论:
- 由TNF-α诱导的IMP,以间隙/JAIL循环为特征,对于中性细胞TEM来说是不可或缺的.
- 酸化MLC和间隙/JAIL循环是IMP和内皮屏障动态的关键调节者.
- 这些发现将IMP调节器确定为炎症疾病的潜在治疗点.
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