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/PLCɣ/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.

中文翻译：

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内皮细胞在内毒素和氧化条件下表现出两波P-选择素表面聚集的波。

败血症是一种临床综合征，其特征在于存在循环的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通路（TLR4 / MyD88 / PI3 K /PLCɣ/ NF-B）激活内皮细胞，从而刺激SELP基因的转录（编码人P-选择素）和P-选择素的释放来自Weibel-Palade机构（WPB）。然而，在24小时内毒素或氧化应激下，内皮细胞中P-选择蛋白表面聚集的时程模式尚未建立。我们的研究表明，P-选择蛋白在细胞表面至少有两个聚集波：一个在内毒素或氧化应激后10分钟，另一个在12小时后聚集。第一波仅取决于WPB传递至细胞膜，而第二波取决于P-选择素翻译机制，ER–Golgi分选，和WPB表面传送。了解内皮细胞中粘附分子的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，以协助脓毒症的治疗。