Distinct Kinetics Features of LFA-1 and Mac-1in 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), Institute of Mechanics, Chinese Academy of Sciences, Center of Biomechanics and Bioengineering, Institute of Mechanics, Chinese Academy of Sciences

出　　处：《Chinese Journal of Biomedical Engineering(English Edition)》2013年第3期105-110,共6页中国生物医学工程学报（英文版）

基　　金：National Natural Science Foundation of China;grant number:30730032,11072251;National Key Basic Research Foundation of China;grant number:2011CB710904

摘　　要：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 were 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 conformations using optical trap technique. Our data indicate 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 on their function differences under shear flow.LFA-1 and Mac-l, two [32 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 leukoeytes rely on LFA-1 while the cell crawling is dependent on Mac-1. We hypothesized that their distinct roles were 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 conformations using optical trap technique. Our data indicate 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 on their function differences under shear flow.

关 键 词：LFA-1 MAC-1 ICAM-1 on-rate off-rate 

分 类 号：R318.01[医药卫生—生物医学工程]