Distinct Kinetics Features of LFA-1 and Mac-1 in Neutrophil Activation  

作　　者：LI Ning MAO De-bin GONG Yi-xin LV Shou-qin ZHANG Yan LONG Mian 

机构地区：[1]Key Laboratory of Microgravity (National Microgravity Laboratory), Center of Biomechanics and Bioengineering,Institute of Mechanics, Chinese Academy of Sciences

出　　处：《Chinese Journal of Biomedical Engineering(English Edition)》2015年第1期40-46,共7页中国生物医学工程学报（英文版）

摘　　要：LFA-1 and Mac-l, two $2 integrin members constitutively expressed on neutrophils, mediate leukocyte recruitment cascade by binding to the same ligand of ICAM-1. The slow rolling and firm adhesion of leukocytes rely on LFA-1 while the cell crawling is dependent on Mac-1. We hypothesized that their distinct roles are likely attributed to the differences in the binding kinetics or in the diverse responses of outside-in and inside-out signaling. In this study, we compared the ICAM-1 binding features between soluble or membrane-expressed LFA-1 and Mac-1 with different affinity conformation using optical trap technique. Our data indicated that the affinity up-regulation from wide type （WT） to high affinity （HA） is off-rate dependent for LFA-1 but on-rate dependent for Mac-1. The structural bases of this new finding were found to be consistent with our previous simulations. These results furthered our understanding in their function differences under shear flow.LFA-1 and Mac-1, two β2integrin members constitutively expressed on neutrophils, mediate leukocyte recruitment cascade by binding to the same ligand of ICAM-1. The slow rolling and firm adhesion of leukocytes rely on LFA-1 while the cell crawling is dependent on Mac-1. We hypothesized that their distinct roles are likely attributed to the differences in the binding kinetics or in the diverse responses of outside-in and inside-out signaling. In this study, we compared the ICAM-1 binding features between soluble or membrane-expressed LFA-1 and Mac-1 with different affinity conformation using optical trap technique. Our data indicated that the affinity up-regulation from wide type(WT) to high affinity(HA) is off-rate dependent for LFA-1but on-rate dependent for Mac-1. The structural bases of this new finding were found to be consistent with our previous simulations. These results furthered our understanding in their function differences under shear flow.

关 键 词：LFA-1 Mac-l ICAM-1 on-rate off-rate 

分 类 号：R318.01[医药卫生—生物医学工程]