E-selectin ligands as mechanosensitive receptors on neutrophils in health and disease.
E-selectin ligands as mechanosensitive receptors on neutrophils in health and disease.
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DOI：
10.1007/s10439-011-0507-y
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发表时间：
2012-04
影响因子：
3.8
通讯作者：
Simon, S. I.
中科院分区：
文献类型：
--
作者：
Chase, S. D.;Magnani, J. L.;Simon, S. I.
将机械力施加到选择素和它们的配体之间的键是这些粘附受体最佳地执行包括白细胞束缚和稳定粘附的激活的功能的要求。尽管所有三种选择素都被报道在配体结合之后从外向内发出信号，但E-选择素在其结合多个唾液酸化Lewisx呈递配体并介导每秒一微米量级的缓慢滚动的能力方面是独特的。小鼠体内的E-选择素识别多种配体，包括ESL-1、CD 44和PSGL-1，它们对于从缓慢滚动到停滞的转变以及有效的跨内皮迁移至关重要。分子识别过程在人类中是不同的，因为L-选择素是主要配体，其沿着糖脂构成人类多形核中性粒细胞（PMN）上超过一半的E-选择素受体。此外，E-选择素在提高CD 18整合素的亲和力和亲合力方面是最有效的，该整合素支持PMN减速和运输到急性炎症部位。该机制仅被部分理解，但已知涉及胞质钙和酪氨酸磷酸化的升高，其激活p38 MAP激酶和Syk激酶，这两者都抑制来自聚集的E-选择素配体的信号。在这篇综述中，我们强调了这个过程的分子识别和机械要求，以揭示E-选择素如何赋予炎症部位外渗信号的选择性和效率，以及针对凝集素结构域的新型糖模拟物拮抗剂的作用机制，该结构域已显示出阻断中性粒细胞活化和粘附在发炎内皮上的功效。
Application of mechanical force to bonds between selectins and their ligands is a requirement for these adhesion receptors to optimally perform functions that include leukocyte tethering and activation of stable adhesion. Although all three selectins are reported to signal from the outside-in subsequent to ligand binding, E-selectin is unique in its capacity to bind multiple sialyl Lewisx presenting ligands and mediate slow rolling on the order of a micron per second. A diverse set of ligands are recognized by E-selectin in the mouse, including ESL-1, CD44, and PSGL-1 which are critical in transition from slow rolling to arrest and for efficient transendothelial migration. The molecular recognition process is different in humans as L-selectin is a major ligand, which along with glycolipids constitute more than half of the E-selectin receptors on human polymorphonuclear neutrophils (PMN). In addition, E-selectin is most efficient at raising the affinity and avidity of CD18 integrins that supports PMN deceleration and trafficking to sites of acute inflammation. The mechanism is only partially understood but known to involve a rise in cytosolic calcium and tyrosine phosphorylation that activates p38 MAP kinase and Syk kinase, both of which transduce signals from clustered E-selectin ligands. In this review we highlight the molecular recognition and mechanical requirements of this process to reveal how E-selectin confers selectivity and efficiency of signaling for extravasation at sites of inflammation and the mechanism of action of a new glycomimetic antagonist targeted to the lectin domain that has shown efficacy in blocking neutrophil activation and adhesion on inflamed endothelium.
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影响因子：
3.2
作者：
Bruehl, RE;Springer, TA;Bainton, DF
通讯作者：
Bainton, DF
影响因子：
15.3
作者：
Cuvelier, SL;Paul, S;Patel, KD
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64.8
作者：
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影响因子：
56.9
作者：
BEVILACQUA, MP;STENGELIN, S;SEED, B
通讯作者：
SEED, B
影响因子：
15.9
作者：
ABBASSI, O;KISHIMOTO, TK;SMITH, CW
通讯作者：
SMITH, CW