期刊
HAEMATOLOGICA
卷 105, 期 7, 页码 1845-1856出版社
FERRATA STORTI FOUNDATION
DOI: 10.3324/haematol.2019.225722
关键词
-
类别
资金
- European Community's Seventh Framework Programme (FP7-2007-2013) [HEALTH-F4-2011-282095]
- Deutsche Forschungsgemeinschaft [SFB 914]
- Else Kroner-Fresenius-Stiftung [2015_A68]
Leukocyte recruitment into inflamed tissue is highly dependent on the activation and binding of integrins to their respective ligands, followed by the induction of various signaling events within the cell referred to as outside-in signaling. Src family kinases (SFK) are the central players in the outside-in signaling process, assigning them a critical role for proper immune cell function. Our study investigated the role of SFK on neutrophil recruitment in vivo using Hck(-/-) Fgr(-/-) Lyn(-/-) mice, which lack SFK expressed in neutrophils. We show that loss of SFK strongly reduces neutrophil adhesion and post-arrest modifications in a shear force dependent manner. Additionally, we found that in the absence of SFK, neutrophils display impaired Rab27a-dependent surface mobilization of neutrophil elastase, VLA3 and VLA6 containing vesicles. This results in a defect in neutrophil vascular basement membrane penetration and thus strongly impaired extravasation. Taken together, we demonstrate that SFK play a role in neutrophil post-arrest modifications and extravasation during acute inflammation. These findings may support the current efforts to use SFK-inhibitors in inflammatory diseases with unwanted neutrophil recruitment.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据