'Slings' enable neutrophil rolling at high shear.
'Slings' enable neutrophil rolling at high shear.
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DOI：
10.1038/nature11248
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发表时间：
2012-08-16
期刊：
影响因子：
64.8
通讯作者：
Ley, Klaus
中科院分区：
文献类型：
--
作者：
Sundd, Prithu;Gutierrez, Edgar;Koltsova, Ekaterina K.;Kuwano, Yoshihiro;Fukuda, Satoru;Pospieszalska, Maria K.;Groisman, Alex;Ley, Klaus
大多数白细胞可以在低切应力(1dyn/cm2)下沿小静脉壁滚动，但在体内，中性粒细胞能够在10倍高的切应力下在微血管中滚动。这种抗剪切滚动涉及的机制是已知的，包括细胞扁平和拉动后面的长膜系绳。在这里，我们展示了这些长系绳并不像假设的那样缩回，而是持续存在，并表现为滚动单元前面的“吊索”。我们在体内急性炎症模型和体外P-选择素模型中展示了吊索，其中P-选择素-糖蛋白-配体-1(PSGL-1)以离散的粘性斑块形式呈现，而LFA-1在吊索上全长表达。随着中性粒细胞向前滚动，吊索包裹在滚动的细胞周围，并通过PSGL-1贴片在流体动力下的失败而从P-选择素底物逐步剥离。“逐步剥离吊衣”与之前报道的“拉系绳”截然不同。每个吊衣有效地在炎症期间以高剪应力滚动的中性粒细胞前面铺设了一个细胞自主粘连底物。
Most leukocytes can roll along the walls of venules at low shear stress (1 dyn/cm2), but neutrophils have the ability to roll at 10-fold higher shear stress in microvessels in vivo. The mechanisms involved in this shear-resistant rolling are known to involve cell flattening and pulling of long membrane tethers at the rear. Here, we show that these long tethers do not retract as postulated, but instead persist and appear as ‘slings’ at the front of rolling cells. We demonstrate slings in a model of acute inflammation in vivo and on P-selectin in vitro, where P-selectin-glycoprotein-ligand-1 (PSGL-1) is presented as discrete sticky patches while LFA-1 is expressed over the entire length on slings. As neutrophils roll forward, slings wrap around the rolling cells and undergo a step-wise peeling from the P-selectin substrate enabled by the failure of PSGL-1 patches under hydrodynamic forces. The ‘step-wise peeling of slings’ is distinct from the ‘pulling of tethers’ reported previously. Each sling effectively lays out a cell-autonomous adhesive substrate in front of neutrophils rolling at high shear stress during inflammation.
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影响因子：
1.1
作者：
Sundd P;Pospieszalska MK;Cheung LS;Konstantopoulos K;Ley K
通讯作者：
Ley K
影响因子：
20.3
作者：
Doyle, Emily L.;Ridger, Victoria;Cutler, Daniel F.
通讯作者：
Cutler, Daniel F.
影响因子：
15.3
作者：
Kunkel, EJ;Jung, U;Ley, K
通讯作者：
Ley, K
影响因子：
20.3
作者：
Kuwano, Yoshihiro;Spelten, Oliver;Zarbock, Alexander
通讯作者：
Zarbock, Alexander
影响因子：
64.8
作者：
Marshall, BT;Long, M;Zhu, C
通讯作者：
Zhu, C