Wang Xiao-Guang, Cheng Yan-Ping, Ba Xue-Qing
Institute of Genetics and Cytology, Northeast Normal University, Changchun 130024, China.
Acta Pharmacol Sin. 2006 May;27(5):617-22. doi: 10.1111/j.1745-7254.2006.00327.x.
The interactions of selectins and their ligands initiate the process of leukocyte migrating into inflamed tissue. P-selectin glycoprotein ligand 1 (PSGL-1) is the best characterized ligand of selectins, and has been demonstrated to mediate the adhesion of leukocytes to all three selectins in vivo. PSGL-1 not only functions as an anchor molecule to capture the leukocytes to the activated endothelial cells by its interaction with selectins, but also transduces the signals to activate leukocytes. Our present work aimed to investigate the mechanism by which PSGL-1-mediated signal activates neutrophils and enhances the adhesion to the endothelial cells.
We detected the effects of the engagement of PSGL-1 with monoclonal antibodies (mAb) or P-selectin on the adhesion of neutrophils to the recombinant intercellular adhesion molecule-1 (ICAM-1), and on the expression of beta(2)-integrin. Additionally, the role of cytoskeleton in these process was studied by using inhibitor cytochalasin B.
The engagement of PSGL-1 increased the expression of beta(2)-integrin on the surface of neutrophils and enhanced the adhesion of neutrophils to the recombinant ICAM-1. mAb against CD18 impaired the adhesion of PSGL-1-engaged neutrophils to ICAM-1. Moreover, the inhibitor cytochalasin B largely blocked the increase of CD18 expression as well as the adhesion of PSGL-1-engaged neutrophils to ICAM-1.
The PSGL-1-transduced signals can enhance beta(2)-integrin-involved adhesion of neutrophils to the recombinant ICAM-1, and this process depends on the dynamics of cytoskeleton.
选择素及其配体的相互作用启动白细胞迁移至炎症组织的过程。P选择素糖蛋白配体1（PSGL-1）是选择素特征最明确的配体，已证实在体内介导白细胞与所有三种选择素的黏附。PSGL-1不仅作为一种锚定分子，通过与选择素相互作用将白细胞捕获到活化的内皮细胞上，还能转导信号激活白细胞。我们目前的工作旨在研究PSGL-1介导的信号激活中性粒细胞并增强其与内皮细胞黏附的机制。
我们检测了PSGL-1与单克隆抗体（mAb）或P选择素结合对中性粒细胞与重组细胞间黏附分子-1（ICAM-1）黏附以及β2整合素表达的影响。此外，通过使用细胞松弛素B抑制剂研究了细胞骨架在这些过程中的作用。
PSGL-1的结合增加了中性粒细胞表面β2整合素的表达，并增强了中性粒细胞与重组ICAM-1的黏附。抗CD18的mAb削弱了PSGL-1结合的中性粒细胞与ICAM-1的黏附。此外，细胞松弛素B抑制剂在很大程度上阻断了CD18表达的增加以及PSGL-1结合的中性粒细胞与ICAM-1的黏附。
PSGL-1转导的信号可增强β2整合素参与的中性粒细胞与重组ICAM-1的黏附，且该过程依赖于细胞骨架的动态变化。
