Ba Xueqing, Chen Cuixia, Gao Yanguang, Zeng Xianlu
Institute of Genetics and Cytology, Northeast Normal University, Changchun 130024, Peoples Republic of China.
J Cell Biochem. 2005 Feb 1;94(2):365-73. doi: 10.1002/jcb.20213.
P-selectin glycoprotein ligand-1 (PSGL-1) is the best-characterized selectin ligand that has been demonstrated to mediate leukocytes rolling on endothelium and leukocytes recruitment into inflamed tissue in vivo. In addition to its direct role in leukocyte capturing, PSGL-1 also functions as a signal-transducing receptor. The present work showed that after cross-linking of PSGL-1 with KPL1, an anti-PSGL-1 monoclonal antibody, PSGL-1 linked to the cytoskeleton and became a detergent-insoluble component in activated neutrophils. The antibody cross-linking led to the polymerization and redistribution of F-actin-based cytoskeleton, and this alteration of cytoskeleton was spatiotemporally related to the polarization of PSGL-1. PSGL-1's polarization was cytoskeleton-dependent because it was eliminated by cytochalasin B. Furthermore, the polymerization and redistribution of F-actin filaments were tyrosine-phosphorylation-dependent since the alteration of F-actin-based cytoskeleton was severely blocked by genistein, a universal tyrosine kinase inhibitor. STI571, a small molecule inhibitor for cytoplasmic tyrosine kinase c-Abl, also inhibited the alteration of F-actin-based cytoskeleton, and c-Abl was redistributed to where F-actin concentrated in the activated neutrophils. The results suggested that cross-linking of PSGL-1 induces the phosphorylation-dependent and c-Abl-involved alteration of F-actin-based cytoskeleton in neutrophils.
P-选择素糖蛋白配体-1（PSGL-1）是特征最明确的选择素配体，已被证明可介导白细胞在内皮上滚动以及白细胞在体内募集到炎症组织中。除了在白细胞捕获中发挥直接作用外，PSGL-1还作为信号转导受体发挥功能。目前的研究表明，用抗PSGL-1单克隆抗体KPL1使PSGL-1交联后，PSGL-1与细胞骨架相连，并在活化的中性粒细胞中成为去污剂不溶性成分。抗体交联导致基于F-肌动蛋白的细胞骨架发生聚合和重新分布，并且这种细胞骨架的改变在时空上与PSGL-1的极化相关。PSGL-1的极化依赖于细胞骨架，因为它被细胞松弛素B消除。此外，F-肌动蛋白丝的聚合和重新分布依赖于酪氨酸磷酸化，因为基于F-肌动蛋白的细胞骨架的改变被染料木黄酮（一种通用的酪氨酸激酶抑制剂）严重阻断。STI571是一种针对细胞质酪氨酸激酶c-Abl的小分子抑制剂，也抑制了基于F-肌动蛋白的细胞骨架的改变，并且c-Abl重新分布到活化中性粒细胞中F-肌动蛋白集中的位置。结果表明，PSGL-1的交联诱导中性粒细胞中基于F-肌动蛋白的细胞骨架发生磷酸化依赖性且涉及c-Abl的改变。
