E-selectin engages PSGL-1 and CD44 through a common signaling pathway to induce integrin αLβ2-mediated slow leukocyte rolling
E-selectin engages PSGL-1 and CD44 through a common signaling pathway to induce integrin αLβ2-mediated slow leukocyte rolling
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DOI：
10.1182/blood-2009-12-259556
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发表时间：
2010-07-22
期刊：
影响因子：
20.3
通讯作者：
McEver, Rodger P.
中科院分区：
文献类型：
--
作者：
Yago, Tadayuki;Shao, Bojing;McEver, Rodger P.
在发炎的小静脉中，在E-选择素上滚动的中性粒细胞通过激活Src家族激酶（SFKs）、DAP 12和Fc受体-γ（FcR γ）、脾酪氨酸激酶（Syk）和p38诱导细胞间粘附分子-1上的整合素α（L）β（2）依赖性缓慢滚动。E-选择素信号传导与趋化因子信号传导协作以将中性粒细胞募集到组织中。先前的研究确定P-选择素糖蛋白配体-1（PSGL-1）是必需的E-选择素配体，Fgr是启动信号传导以减慢滚动的唯一SFK。相反，我们发现E-选择素与PSGL-1或CD 44的结合通过一个共同的脂筏依赖性途径触发缓慢滚动，该途径使用SFKs Hck和林恩以及Fgr。我们确定Tec激酶布鲁顿酪氨酸激酶是Syk和p38之间的关键信号中间体。PSGL-1的E-选择素参与依赖于其胞质结构域来激活SFKs和缓慢滚动。尽管据报道将磷酸肌醇-3-激酶募集到PSGL-1胞质结构域激活整联蛋白，但E-选择素介导的慢滚动不需要磷酸肌醇-3-激酶。在小鼠中的研究证实了这些事件对于炎症期间中性粒细胞缓慢滚动和募集的生理意义。因此，E-选择素通过不同的中性粒细胞糖蛋白触发共同信号，诱导α（L）β（2）依赖性慢滚动。（血。2010; 116（3）：485-494）
In inflamed venules, neutrophils rolling on E-selectin induce integrin alpha(L)beta(2)-dependent slow rolling on intercellular adhesion molecule-1 by activating Src family kinases (SFKs), DAP12 and Fc receptor-gamma (FcR gamma), spleen tyrosine kinase (Syk), and p38. E-selectin signaling cooperates with chemokine signaling to recruit neutrophils into tissues. Previous studies identified P-selectin glycoprotein ligand-1 (PSGL-1) as the essential E-selectin ligand and Fgr as the only SFK that initiate signaling to slow rolling. In contrast, we found that E-selectin engagement of PSGL-1 or CD44 triggered slow rolling through a common, lipid raft-dependent pathway that used the SFKs Hck and Lyn as well as Fgr. We identified the Tec kinase Bruton tyrosine kinase as a key signaling intermediate between Syk and p38. E-selectin engagement of PSGL-1 was dependent on its cytoplasmic domain to activate SFKs and slow rolling. Although recruiting phosphoinositide-3-kinase to the PSGL-1 cytoplasmic domain was reported to activate integrins, E-selectin-mediated slow rolling did not require phosphoinositide-3-kinase. Studies in mice confirmed the physiologic significance of these events for neutrophil slow rolling and recruitment during inflammation. Thus, E-selectin triggers commonsignals through distinct neutrophil glycoproteins to induce alpha(L)beta(2)-dependent slow rolling. (Blood. 2010; 116(3): 485-494)