Epinephrine Modulates BCAM/Lu and ICAM-4 Expression on the Sickle Cell Trait Red Blood Cell Membrane

Epinephrine Modulates BCAM/Lu and ICAM-4 Expression on the Sickle Cell Trait Red Blood Cell Membrane
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DOI:
10.1016/j.bpj.2012.01.050
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发表时间:
2012-03-07
影响因子:
3.4
通讯作者:
Lykotrafitis, George
Lykotrafitis, George
中科院分区:
生物学3区
文献类型:
--
作者:
Maciaszek, Jamie L.;Andemariam, Biree;Lykotrafitis, George

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体能训练中的虚脱和猝死是镰状细胞病最严重的并发症。有证据表明,SCT患者中的红细胞在剧烈运动期间聚集,这可能是由于与细胞外基质(ECM)和内皮细胞的粘附相互作用,以及由于其不规则的粘弹性。这导致炎症、血流障碍和血管闭塞事件。然而,压力条件的确切作用以及它们如何导致这些并发症几乎是未知的。使用单分子原子力显微镜实验,我们发现肾上腺素,一种在应激条件下分泌的激素,与未受刺激的SCT红细胞相比,增加了基底细胞粘附分子(BCAM/Lu)和ECM层粘连蛋白之间以及细胞间粘附分子-4(ICAM-4)和内皮细胞α(v)β(3)之间粘附事件的频率和强度。粘附频率的增加为肾上腺素在BCAM/Lu-层粘连蛋白和ICAM-4-α(v)β(3)结合中的作用提供了重要证据,并提示了SCT中体力消耗期间血管闭塞的机制。
Collapse and sudden death in physical training are the most serious complications of sickle cell trait (SCT). There is evidence that erythrocytes in SCT patients aggregate during strenuous exercise, likely because of adhesive interactions with the extracellular matrix (ECM) and endothelial cells, and because of their irregular viscoelastic properties. This results in inflammation, blood flow impairment, and vaso-occlusive events. However, the exact role of stress conditions and how they lead to these complications is virtually unknown. Using single-molecule atomic force microscopy experiments, we found that epinephrine, a hormone that is secreted under stressful conditions, increases both the frequency and strength of adhesion events between basal cell adhesion molecule (BCAM/Lu) and ECM laminin, and between intercellular adhesion molecule-4 (ICAM-4) and endothelial alpha(v)beta(3), compared with nonstimulated SCT erythrocytes. Increases in adhesion frequency provide significant evidence of the role of epinephrine in BCAM/ Lu-laminin and ICAM-4-alpha(v)beta(3) bonding, and suggest mechanisms of vaso-occlusion during physical exertion in SCT.