Department of Mechanical Engineering, University of Connecticut, Storrs, Connecticut, USA.
Biophys J. 2012 Mar 7;102(5):1137-43. doi: 10.1016/j.bpj.2012.01.050. Epub 2012 Mar 6.
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 α(v)β(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-α(v)β(3) bonding, and suggest mechanisms of vaso-occlusion during physical exertion in SCT.
在体能训练中，镰状细胞特征（SCT）患者最严重的并发症是崩溃和猝死。有证据表明，在剧烈运动期间，SCT 患者的红细胞聚集，这可能是由于与细胞外基质（ECM）和内皮细胞的黏附相互作用，以及由于其不规则的粘弹性特性。这会导致炎症、血流受损和血管阻塞事件。然而，应激条件的确切作用以及它们如何导致这些并发症实际上是未知的。使用单分子原子力显微镜实验，我们发现，肾上腺素是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，它增加了基底细胞黏附分子（BCAM/Lu）和 ECM 层粘连蛋白之间以及细胞间黏附分子-4（ICAM-4）和内皮细胞 α(v)β(3)之间黏附事件的频率和强度。黏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)键合中的作用提供了重要证据，并表明了 SCT 患者在体力活动期间发生血管阻塞的机制。
