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Abstract：
Chronic spontaneous urticaria (CSU) is characterized by daily recurring wheal and flare with itch for more than 6 weeks. The extrinsic coagulation system has been shown to be activated in correlation with CSU severity. We have reported that tissue factor (TF), a trigger of the extrinsic coagulation cascade, is synergistically expressed on vascular endothelial cells by simultaneous stimulation with TF inducers (TFI), followed by activation of the extrinsic coagulation cascade and hyper permeability in vitro. However, vascular endothelial cells are not likely to be simultaneously stimulated by multiple TFIs under physiological conditions. Therefore, in order to know whether sequential, rather than simultaneous, stimuli with interval may induce synergistic activation of TF, we investigated the time course of the priming effects of each TFI for synergistic TF expression in vascular endothelial cells (HUVECs). We stimulated HUVECs with a TFI (first stimulation) and then stimulated cells with another TFI at indicated time points (second stimulation) and detected TF expression and activity. The TF expression induced by simultaneous stimulation diminished in a few hours. However, both synergistic enhancement of TF expression and activation level of the coagulation cascade were detected even when the second stimulation was added 18 or 22 h after the first stimulation. Thus, the priming effect of TFI for synergistic TF expression may persist for a half day or longer.
摘要：
慢性自发性荨麻疹（CSU）的特征是每天反复发作的风团和瘙痒发作超过6周。已显示外源性凝血系统与CSU严重程度相关而被激活。我们已经报道了组织因子（TF），外源性凝血级联的触发因素，通过与TF诱导剂（TFI）同时刺激在血管内皮细胞上协同表达，随后在体外激活外源性凝血级联和高通透性。然而,在生理条件下，血管内皮细胞不太可能同时受到多个TFI的刺激。因此,为了知道是否连续，而不是同时，有间隔的刺激可能诱导TF的协同激活，我们研究了每种TFI对血管内皮细胞（HUVECs）中协同TF表达的启动作用的时程。我们用TFI刺激HUVEC(第一次刺激),然后在指定时间点(第二次刺激)用另一种TFI刺激细胞,并检测TF表达和活性。同时刺激诱导的TF表达在数小时内减少。然而,即使在第一次刺激后18或22小时添加第二次刺激，也可以检测到TF表达的协同增强和凝血级联的激活水平。因此，TFI对协同TF表达的启动作用可能持续半天或更长时间。
