Endothelial Cells Exhibit Two Waves of P-selectin Surface Aggregation Under Endotoxic and Oxidative Conditions
Endothelial Cells Exhibit Two Waves of P-selectin Surface Aggregation Under Endotoxic and Oxidative Conditions
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DOI：
10.1007/s10930-019-09865-0
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发表时间：
2019-12-01
期刊：
影响因子：
3
通讯作者：
Simon, Felipe
中科院分区：
文献类型：
--
作者：
Barrionuevo, Nathaly;Gatica, Sebastian;Simon, Felipe
脓毒症是一种临床综合征，其特征是存在循环微生物内毒素和氧化应激。内毒素和氧化应激通过会聚信号传导途径（TLR 4/MyD 88/PI 3 K/PLC γ/NF-B）激活内皮细胞，所述会聚信号传导途径刺激SELP基因（其编码人P-选择素）的转录和P-选择素从韦伯-帕拉德体（WPB）的释放。然而，在内皮细胞内毒素或氧化应激24小时下，尚未建立P-选择素表面聚集的时程模式。我们的研究表明，P-选择素在细胞表面至少有两个聚集波：一个10分钟，另一个12小时后内毒素或氧化应激。第一波完全依赖于WPB递送到细胞膜，而第二波依赖于P-选择素翻译机制、ER-高尔基体分选和WPB表面递送。了解内皮细胞中的粘附分子动力学可以提供进一步的分子见解，以开发诊断或治疗工具，以帮助管理脓毒症。
Sepsis is a clinical syndrome characterized by the presence of circulating microbial endotoxins and oxidative stress. Endotoxin and oxidative stress activate endothelial cells via a convergent signaling pathway (TLR4/MyD88/PI3 K/PLC gamma/NF-B) that stimulates both the transcription of SELP gene (which encodes for human P-selectin) and the release of P-selectin from Weibel-Palade bodies (WPBs). However, time course pattern of P-selectin surface aggregation has not been established in endothelial cells under 24 h of endotoxic or oxidative stress. Our study shows that P-selectin has at least two waves of aggregation at the cell surface: one 10 min and the other 12 h after endotoxic or oxidative stress. The first wave depends exclusively on WPB delivery to the cell membrane, while the second depends on P-selectin translation machinery, ER-Golgi sorting, and WPB surface delivery. Understanding adhesion molecule dynamics in endothelial cells could provide further molecular insights to develop diagnostic or therapeutic tools to aid in the management of sepsis.