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。
Objective To explore the activate process of lymphocyte function-associated antigen 1（ LFA-1） triggered by chemokine under shear stresses. Methods Jurkat cells were perfused over ICAM-1 in the parallel-plate flow under 10-30 m Pa shear stresses. The effects of soluble and immobilized Chemokines on transient adhesion behavior of Jurkat cells were observed and analyzed to obtain their tether characteristics. Results The immobilized CXCL12 could mediate brief tether（ 0. 13-0. 2 s） of Jurkat cells under flow. Only immobilized CXCL12 could effectively activate LFA-1 on Jurkat cells to bind ICAM-1,and then enhance cell adhesion fraction and greatly prolong the tether time（ 0. 8-1. 2 s）. Two distinct activation states of LFA-1/ICAM-1 were reflected by their dissociation rate k1（ 1. 09-1. 24 s^-1） and k2（ 0. 28-0. 7 s^-1）,respectively. The shear stress would affect the transient adhesion behavior of cells through regulation of k2 and β（ the contribution ratio of high affinity to total tether time）.Conclusions Shear stress can rapidly trigger LFA-1 activation in 0. 2 s through G protein coupled receptors induced by chemokine CXCL12,and further regulate the whole adhesion process of leukocyte. These research findings will contribute to further understanding the integrin activation mechanism of chemokine-force cooperative regulation.
出处
《医用生物力学》
EI
CAS
CSCD
北大核心
2017年第6期548-554,共7页
Journal of Medical Biomechanics
基金
国家自然科学基金项目(11432006,11672109,11272125,31170887)
