Sphingosine-1-phosphate receptor 3 promotes leukocyte rolling by mobilizing endothelial P-selectin.
Sphingosine-1-phosphate receptor 3 promotes leukocyte rolling by mobilizing endothelial P-selectin.
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鞘氨醇1-磷酸受体3通过动员内皮P-选择素促进白细胞滚动。
DOI：
10.1038/ncomms7416
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发表时间：
2015-04-02
影响因子：
16.6
通讯作者：
Levkau, Bodo
中科院分区：
文献类型：
--
作者：
Nussbaum, Claudia;Bannenberg, Sarah;Keul, Petra;Graeler, Markus H.;Goncalves-de-Albuquerque, Cassiano F.;Korhonen, Hanna;Lipinski, Karin von Wnuck;Heusch, Gerd;de Castro Faria Neto, Hugo C.;Rohwedder, Ina;Goethert, Joachim R.;Prasad, Vysakh Pushpa;Haufe, Guenter;Lange-Sperandio, Baerbel;Offermanns, Stefan;Sperandio, Markus;Levkau, Bodo
鞘氨醇-1-磷酸（S1 P）参与炎症;然而，其在白细胞滚动中的作用仍不清楚。我们在炎症小鼠提睾肌小静脉和人内皮细胞中使用活体显微镜，显示S1 P通过内皮S1 P受体3（S1 P3）和Gαq、PLCβ和Ca 2+促进P-选择素依赖性白细胞滚动。动脉内给予S1 P可增加白细胞滚动，而S1 P3缺陷或抑制可显着减少白细胞滚动。参与触发滚动的肥大细胞也会释放S1 P，通过S1 P3动员P-选择素。组胺和肾上腺素需要S1 P3通过刺激鞘氨醇激酶1（Sphk 1）来实现全面效应。在内皮特异性S1 P1 −/−小鼠中观察到，S1 P1以反调节方式抑制cAMP刺激的Sphk 1并阻断滚动。与S1 P3的显性促滚动效应一致，FTY 720抑制对照和S1 P1 −/−小鼠的滚动，但不抑制S1 P3 −/−小鼠的滚动。我们的研究结果确定S1 P作为白细胞滚动的直接和间接贡献者，并表征介导其作用的受体。 已知脂质鞘氨醇-1-磷酸（S1 P）介导炎症中的白细胞募集。在此，Nussbaum等人表明，S1 P通过其受体S1 P3，也通过促进粘附分子P-选择素在内皮表面上的呈递来调节内皮上的白细胞滚动。
Sphingosine-1-phosphate (S1P) participates in inflammation; however, its role in leukocyte rolling is still unclear. Here we use intravital microscopy in inflamed mouse cremaster muscle venules and human endothelial cells to show that S1P contributes to P-selectin-dependent leukocyte rolling through endothelial S1P receptor 3 (S1P3) and Gαq, PLCβ and Ca2+. Intra-arterial S1P administration increases leukocyte rolling, while S1P3 deficiency or inhibition dramatically reduces it. Mast cells involved in triggering rolling also release S1P that mobilizes P-selectin through S1P3. Histamine and epinephrine require S1P3 for full-scale effect accomplishing it by stimulating sphingosine kinase 1 (Sphk1). In a counter-regulatory manner, S1P1 inhibits cAMP-stimulated Sphk1 and blocks rolling as observed in endothelial-specific S1P1−/− mice. In agreement with a dominant pro-rolling effect of S1P3, FTY720 inhibits rolling in control and S1P1−/− but not in S1P3−/− mice. Our findings identify S1P as a direct and indirect contributor to leukocyte rolling and characterize the receptors mediating its action. The lipid sphingosine-1-phosphate (S1P) is known to mediate leukocyte recruitment in inflammation. Here, Nussbaum et al. show that S1P, via its receptor S1P3, also regulates leukocyte rolling on endothelium by promoting the presentation of the adhesion molecule P-selectin on the endothelial surface.
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影响因子：
4.8
作者：
Kimura, T;Tomura, H;Okajima, F
通讯作者：
Okajima, F
DOI：
10.1084/jem.20082502
发表时间：
2009-04-13
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Gossens K;Naus S;Corbel SY;Lin S;Rossi FM;Kast J;Ziltener HJ
通讯作者：
Ziltener HJ
影响因子：
15.3
作者：
Kunkel, EJ;Jung, U;Ley, K
通讯作者：
Ley, K
鞘氨醇 1-磷酸受体 1 通过抑制外周组织 T 淋巴细胞进入传入淋巴管而导致组织滞留
影响因子：
30.5
作者：
Ledgerwood, Levi G.;Lal, Girdhari;Bromberg, Jonathan S.
通讯作者：
Bromberg, Jonathan S.
DOI：
10.1161/01.atv.0000154360.36106.d9
发表时间：
2005-03-01
影响因子：
8.7
作者：
Krump-Konvalinkova, V;Yasuda, S;Siess, W
通讯作者：
Siess, W