流体剪应力作用下趋化因子CXCL12诱导的白细胞整合素LFA-1的激活

发布时间：2018-02-15 12:32

本文关键词： 白细胞整合素LFA- 趋化因子CXCL 亲和态跃迁受体配体相互作用细胞黏附　出处：《医用生物力学》2017年06期 　论文类型：期刊论文

【摘要】：目的探究剪应力下趋化因子诱导的白细胞上整合素LFA-1激活过程。方法采用平行平板流动腔系统在10~30 mPa剪应力下,观察分析可溶性及固定趋化因子CXCL12对Jurkat细胞在ICAM-1上瞬时黏附行为的影响,提取特征参数。结果 CXCL12仅能介导Jurkat细胞的短暂栓缚(0.13~0.20 s)。只有固定的CXCL12才能有效激活Jurkat细胞上LFA-1与ICAM-1键合,从而提高栓缚事件的发生率,并大大延长细胞的栓缚时间(0.8~1.2 s)。激活的LFA-1/ICAM-1解离速率呈现明显双态性:k_1(1.09~1.24 s~(-1)),k_2(0.28~0.7 s~(-1)),剪应力主要通过调节k_2及k_2对整个黏附时间的贡献率β来控制细胞的瞬时黏附行为。结论剪应力通过G蛋白偶联受体与CXCL12的作用可在0.2 s内快速激活整合素LFA-1,进而调控白细胞的黏附过程。研究结果有助于深化趋化因子-力偶联调控整合素激活机制的认识。
[Abstract]:Objective to investigate the activation process of integrin LFA-1 on leukocytes induced by chemokines under shear stress. The effects of soluble and immobilized chemokine CXCL12 on transient adhesion of Jurkat cells on ICAM-1 were observed and analyzed. Results CXCL12 could only mediate the transient binding of Jurkat cells 0.13 ~ 0.20 s 路s ~ (-1). Only fixed CXCL12 could effectively activate the binding of LFA-1 and ICAM-1 on Jurkat cells, thus increasing the incidence of binding events. The activated LFA-1/ICAM-1 dissociation rate was significantly bimodal: K11.09 / 1.24 s-1 / L ~ (-1). The shear stress was mainly controlled by adjusting the contribution rate 尾 of k2 and kSn2 to the whole adhesion time. The effect of shear stress on the transient adhesion behavior of the cells was studied by adjusting the effect of K _ 2 and K _ S _ 2 on the transient adhesion behavior of the cells to the whole adhesion time (尾), and to control the transient adhesion behavior of the cells by adjusting the ratio of K _ 2 and K _ S _ 2 contribution to the whole adhesion time. It is suggested that shear stress can rapidly activate integrin LFA-1 and regulate the adhesion process of leukocytes in 0.2 s through the interaction of G protein-coupled receptors with CXCL12. The results of this study are helpful to deepen the understanding of chemokine-coupled regulation mechanism of integrin activation.
【作者单位】：华南理工大学生物科学与工程学院生物力学研究所;
【基金】：国家自然科学基金项目(11432006,11672109,11272125,31170887)
【分类号】：R318.01

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