流体剪切力下趋化因子CXCL12诱导的Jurkat T细胞的钙响应
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1.华南理工大学 生物科学与工程学院;2.华南理工大学 生物科学与工程学院 生物力学研究所

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国家自然科学基金(11672109,11432006,11272125,31170887)


Chemokine CXCL12 induced calcium response of Jurkat T cells under fluid shear stress
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Institute of Biomechanics,School of Bioscience and Bioengineering,South China University of Technology

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    摘要:

    目的 探究流体剪切应力条件下趋化因子诱导Jurkat T细胞钙响应的力-化学耦合调控机制。方法 通过流动腔系统与荧光显微镜结合,在静止或流场条件下,观察分析有或无胞外钙离子时固定化趋化因子CXCL12诱导的Jurkat T细胞钙响应过程,提取相应特征参数。结果 CXCL12可以介导Jurkat T细胞的稳定黏附且呈现浓度依赖性;力是细胞钙响应的开关,当流体剪切力从0提高到20 mPa时,钙响应激活比率从约4%提高到约75%;在20 mPa剪切力下,胞外钙离子可以通过缩短延迟时间(缩短约23 s)加快钙响应,增加爬坡时间(约7 s)和半衰期(约20 s)提高钙响应强度。结论 流体剪应力和胞外钙离子协同作用,加快、加强了CXCL12介导的Jurkat T细胞钙响应,提示一条依赖MS通道的“外钙内流—内质网钙库释放”的快速通路。该研究结果有助于深入理解T细胞的活化过程,为相应病理和药物研究提供参考。

    Abstract:

    Objective To investigate the Force-chemical coupling regulation mechanism of chemokine-induced calcium response in Jurkat T cells under fluid shear stress. Methods With the combination of flow chamber and flourescence microscope calcium response in Jurkat T cells, stained with Fluo-4 AM, was observed with or without extracellular calcium ions under fluid shear stress. Corresponding characteristic parametres were extracted. Results CXCL12 could induce firm adhesion of Jurkat T cells in a concentration-dependent manner. Force was the key to start calcium response. When the fluid shear force increased from 0 to 20 mPa, activation ratio rouse up to 75% from 4%. Under fluid shear stress of 20 mPa, extracellular calcium ions could speed the process of calcium response by shortening delay time (about 23 s), prolong half time (about 7 s) and half time (about 20 s) and strengthen intensity. Conclusions Fluid shear stress and extracellular calcium ions synergize to accelerate and enhance CXCL12-mediated calcium response in Jurkat T cells, suggesting a fast ‘extracellular calcium influx-intracellular calcium store release’ pathway which shows MS dependence. This study can deepen the understanding T cells activation and provide reference for relevant pathological and drug research.

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  • 收稿日期:2019-04-08
  • 最后修改日期:2019-06-04
  • 录用日期:2019-07-03
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