IL-8-induced L-selectin shedding regulates its binding kinetics to PSGL-1 |
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Authors: | XiaoLing Jia Juan Chen Mian Long |
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Institution: | (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 |
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Abstract: | 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.
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)
and National High-Tech Research and Development Program of China (Grant No. 2007AA02Z306) |
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Keywords: | L-selectin shedding PSGL-1 kinetics reverse and forward rates IL-8 |
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