Complete identification of E-selectin ligands on neutrophils reveals distinct functions of PSGL-1, ESL-1, and CD44
Complete identification of E-selectin ligands on neutrophils reveals distinct functions of PSGL-1, ESL-1, and CD44
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DOI：
10.1016/j.immuni.2007.03.011
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发表时间：
2007-04-01
期刊：
影响因子：
32.4
通讯作者：
Frenette, Paul S.
中科院分区：
文献类型：
--
作者：
Hidalgo, Andres;Peired, Anna J.;Frenette, Paul S.
选择素及其配体是炎症过程中白细胞外渗所必需的。一些糖蛋白已被建议在体外结合E-选择素，但其生理配体的完整鉴定仍然难以捉摸。在此，我们通过基因和RNA靶向功能丧失，发现E-选择素配体-1（埃西尔-1）、P-选择素糖蛋白配体-1（PSGL-1）和CD 44包含了中性粒细胞上所有内皮选择素配体活性。PSGL-1在初始白细胞捕获中起主要作用，而ESL-1对于将初始束缚转化为稳定的缓慢滚动至关重要。CD 44通过p38信号控制滚动速度并介导PSGL-1和L-选择素的E-选择素依赖性再分布到缓慢滚动的白细胞上的主要极点。这些结果表明，这三种糖蛋白在选择素介导的中性粒细胞粘附和信号传导中具有不同的动态贡献。
The selectins and their ligands are required for leukocyte extravasation during inflammation. Several glycoproteins have been suggested to bind to E-selectin in vitro, but the complete identification of its physiological ligands has remained elusive. Here, we showed that E-selectin ligand-1 (ESIL-1), P-selectin glycoprotein ligand-1 (PSGL-1), and CD44 encompassed all endothelial-selectin ligand activity on neutrophils by using gene- and RNA-targeted loss of function. PSGL-1 played a major role in the initial leukocyte capture, whereas ESL-1 was critical for converting initial tethers into steady slow rolling. CD44 controlled rolling velocity and mediated E-selectin-dependent redistribution of PSGL-1 and L-selectin to a major pole on slowly rolling leukocytes through p38 signaling These results suggest distinct and dynamic contributions of these three glycoproteins in selectin-mediated neutrophil adhesion and signaling.