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.
基金
National Natural Science Foundation of China
grant number:30730032,11072251
National Key Basic Research Foundation of China
grant number:2011CB710904
