流体剪切力下趋化因子CXCL12诱导Jurkat T细胞的钙响应机制
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国家自然科学基金项目(11672109,11702100,11432006,11272125)


Chemokine CXCL12-Induced Calcium Response of Jurkat T Cells under Fluid Shear Stress
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    摘要:

    目的 探究流体剪切力(fluid shear stress, FSS)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Ca2+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FSS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 FSS下,胞外Ca2+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 FSS和胞外Ca2+协同作用,加快、加强CXCL12介导的Jurkat T细胞钙响应,提示一条依赖机械敏感钙离子通道的“外钙内流-内质网钙库释放”的快速通路。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 mechanism of mechano-chemical coregulation in chemokine-induced calcium response of Jurkat T cells under fluid shear stress (FSS). Methods By using parallel-plate flow chamber combined with fluorescence microscope, the calcium response of Jurkat T cells on CXCL12 was observed to extract the corresponding characteristic parameters under static or flow state, with or without extracellular Ca2+, respectively. Results Immobilized CXCL12 could induce firm adhesion of the circulating Jurkat T cells, and the arrested cells increased with the increase of CXCL12 concentration. Force could trigger the calcium response of Jurkat T cells and sharply raised the activation ratio from 4% up to 75% when the FSS increased from 0 to 20 mPa. Under 20 mPa FSS, extracellular Ca2+ could stimulate quickly the calcium response by shortening the delay time (about 23 s), and enhance calcium intensity by prolonging the climbing time (about 7 s) and half time (about 20 s). Conclusions The cooperation between FSS and extracellular Ca2+ would accelerate and enhance CXCL12-mediated-calcium response of Jurkat T cells, which indicated a fast mechanosensitive pathway through ‘extracellular calcium influx-intracellular calcium store release’. The research results would contribute to understanding the process of T cells activation and providing the clue for relevant pathological and drug research.

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胡兵,吴建华,凌颖琛,方颖.流体剪切力下趋化因子CXCL12诱导Jurkat T细胞的钙响应机制[J].医用生物力学,2020,35(3):331-337

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  • 收稿日期:2019-04-08
  • 最后修改日期:2019-06-04
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  • 在线发布日期: 2020-06-24
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