E-selectin engages PSGL-1 and CD44 through a common signaling pathway to induce integrin αLβ2-mediated slow leukocyte rolling

Tadayuki Yago, Bojing Shao, Jonathan J. Miner, Longbiao Yao, Arkadiusz G. Klopocki, Kenichiro Maeda, K. Mark Coggeshall, Rodger P. McEver

Research output: Contribution to journalArticlepeer-review

152 Scopus citations

Abstract

In inflamed venules, neutrophils rolling on E-selectin induce integrin αLβ2-dependent slow rolling on intercellular adhesion molecule-1 by activating Src family kinases (SFKs), DAP12 and Fc receptor-γ (FcRγ), 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 common signals through distinct neutrophil glycoproteins to induce αLβ2-dependent slow rolling.

Original languageEnglish
Pages (from-to)485-494
Number of pages10
JournalBlood
Volume116
Issue number3
DOIs
StatePublished - Jul 22 2010

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