ヒト血管内皮細胞における相乗的組織因子発現に対する組織因子誘発物質の時間解析

抄録

Chronic spontaneous urticaria (CSU) is known as 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 in response to simultaneous stimulation with TF-inducers, such as LPS and histamine. However, vascular endothelial cells are not likely to be stimulated simultaneously with TF inducers in physiological conditions. Therefore, we here investigated the priming effects of each TF inducer for synergistic TF expression in vascular endothelial cells (HUVECs). We stimulated HUVECs with a TF-inducer (first stimulation) and then stimulated cells with another TF-inducer at indicated time points (second stimulation), and detected TF expression and activity. The TF expression induced by simultaneous stimulation diminished in few hours. However, both synergistic increase of TF expression and activation of coagulation cascade were observed even when the second stimulation was added 18 hours after the first stimulation. Thus, the priming effect of TF-inducer for synergistic TF expression and activation may persist for a day or longer.