IL-8-induced L-selectin shedding regulates its binding kinetics to PSGL-1  

作　　者：JIA XiaoLing1,2,3, CHEN Juan1,2 & LONG Mian1,2 1 National Microgravity Laboratory, Institute of Mechanics, Chinese Academy of Sciences, Beijing 100190, China 2 Center of Biomechanics and Bioengineering, Institute of Mechanics, Chinese Academy of Sciences, Beijing 100190, China 3 School of Biological Science and Medical Engineering, Beihang University, Beijing 100083, China 

出　　处：《Chinese Science Bulletin》2009年第16期2786-2793,共8页

基　　金：Supported by the National Basic Research Program of China (Grant No. 2006CB910303);National Natural Science Foundation of China (Grant Nos. 30730032, 10332060);Knowledge Innovation Program of Chinese Academy of Sciences (Grant No. KJCX2-YW-L08);National High-Tech Research and De-velopment Program of China (Grant No. 2007AA02Z306)

摘　　要：L-selectin plays a crucial role in inflammation cascade by initiating the tethering and rolling of leukocytes on endothelium wall. While many L-selectin molecules are rapidly shed from the cell surface upon activation, the remaining membrane-anchored L-selectin may still play an important role in regulating leukocyte rolling and adhesion with different binding kinetics. Here we developed an in vitro model to activate Jurkat cells via interlukin-8 (IL-8) and quantified the two-dimensional (2D) binding kinetics, using a micropipette aspiration assay, of membrane-anchored L-selectin to P-selectin glycoprotein ligand 1 (PSGL-1) ligand coupled onto human red blood cells (RBCs). The data indicated that L-selectin shedding reduced the amount of membrane-anchored L-selectin and lowered both its reverse and forward rates. These results suggested that the rolling dynamics of activated leukocytes was determined by two opposite impacts: reducing the surface presentation would enhance the rolling but lowering the kinetic rates would decrease the rolling. This finding provides a new insight into under-standing how L-selectin shedding regulates leukocyte rolling and adhesion.L-selectin plays a crucial role in inflammation cascade by initiating the tethering and rolling of leukocytes on endothelium wall. While many L-selectin molecules are rapidly shed from the cell surface upon activation, the remaining membrane-anchored L-selectin may still play an important role in regulating leukocyte rolling and adhesion with different binding kinetics. Here we developed an in vitro model to activate Jurkat cells via interlukin-8 （IL-8） and quantified the two-dimensional （2D） binding kinetics, using a micropipette aspiration assay, of membrane-anchored L-selectin to P-selectin glycoprotein ligand 1 （PSGL-1） ligand coupled onto human red blood cells （RBCs）. The data indicated that L-selectin shedding reduced the amount of membrane-anchored L-selectin and lowered both its reverse and forward rates. These results suggested that the rolling dynamics of activated leukocytes was determined by two opposite impacts： reducing the surface presentation would enhance the rolling but lowering the kinetic rates would decrease the rolling. This finding provides a new insight into understanding how L-selectin shedding regulates leukocyte rolling and adhesion.

关 键 词：结合动力学 选择素 配体 白细胞介素8 JURKAT细胞 诱导 细胞表面 微管吸吮 

分 类 号：R363[医药卫生—病理学]