GEF-H1 is necessary for neutrophil shear stress-induced migration during inflammation.
GEF-H1 is necessary for neutrophil shear stress-induced migration during inflammation.
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DOI：
10.1083/jcb.201603109
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发表时间：
2016-10-10
期刊：
影响因子：
--
通讯作者：
Rottapel R
中科院分区：
文献类型：
--
作者：
Fine N;Dimitriou ID;Rullo J;Sandí MJ;Petri B;Haitsma J;Ibrahim H;La Rose J;Glogauer M;Kubes P;Cybulsky M;Rottapel R
在他们的工作中，Fine等人证明了GEF-H1是中性粒细胞响应血管内血流而扩散和爬行所必需的。他们揭示了一种新的机制，耦合剪切应力与Rho依赖性迁移行为的中性粒细胞在炎症。血液流动产生的剪切应力可增强白细胞的爬行和跨内皮迁移。耦合剪切应力迁移的机制尚未完全阐明。我们发现，缺乏GEF-H1（GEF-H1−/−）的小鼠，一种RhoA特异性鸟嘌呤核苷酸交换因子（GEF），表现出有限的中性粒细胞迁移和招募到炎症组织中。GEF-H1−/−白细胞在体内爬行和毛细血管后小静脉中的TEM中缺乏。我们证明，虽然GEF-H1缺乏对中性粒细胞在静态条件下的迁移特性的影响不大，剪切应力触发GEF-H1依赖的蔓延和爬行的中性粒细胞和重新定位的GEF-H1的flotillin-2丰富的uropod。我们的研究结果确定GEF-H1作为中性粒细胞的剪切应力反应机制的一个组成部分，需要一个完全胜任的细菌感染的免疫反应。
In their work, Fine et al. demonstrate that GEF-H1 is required for the spreading and crawling of neutrophils in response to intravascular blood flow. They uncover a novel mechanism that couples shear stress with Rho-dependent migratory behavior of neutrophils during inflammation. Leukocyte crawling and transendothelial migration (TEM) are potentiated by shear stress caused by blood flow. The mechanism that couples shear stress to migration has not been fully elucidated. We found that mice lacking GEF-H1 (GEF-H1−/−), a RhoA-specific guanine nucleotide exchange factor (GEF), displayed limited migration and recruitment of neutrophils into inflamed tissues. GEF-H1−/− leukocytes were deficient in in vivo crawling and TEM in the postcapillary venules. We demonstrated that although GEF-H1 deficiency had little impact on the migratory properties of neutrophils under static conditions, shear stress triggered GEF-H1–dependent spreading and crawling of neutrophils and relocalization of GEF-H1 to flotillin-2–rich uropods. Our results identify GEF-H1 as a component of the shear stress response machinery in neutrophils required for a fully competent immune response to bacterial infection.
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影响因子：
4.4
作者：
Cinamon, G;Shinder, V;Alon, R
通讯作者：
Alon, R
影响因子：
21.3
作者：
Krendel, M;Zenke, FT;Bokoch, GM
通讯作者：
Bokoch, GM
影响因子：
56.9
作者：
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通讯作者：
Butcher, EC
DOI：
10.1016/j.bbrc.2008.01.066
发表时间：
2008-03-28
影响因子：
3.1
作者：
Fujishiro, Shuh-hei;Tammura, Susumu;Kohno, Michiaki
通讯作者：
Kohno, Michiaki
DOI：
10.1083/jcb.201002067
发表时间：
2010-08-23
期刊：
The Journal of cell biology
影响因子：
--
作者：
Heasman SJ;Carlin LM;Cox S;Ng T;Ridley AJ
通讯作者：
Ridley AJ