Chen Lien-Cheng, Shyu Huey-Wen, Lin Hui-Min, Lei Huan-Yao, Lin Yee-Shin, Liu Hsiao-Sheng, Yeh Trai-Ming
Institute of Basic Medical Sciences, National Cheng Kung University, Tainan, Taiwan, ROC.
J Infect. 2009 May;58(5):368-74. doi: 10.1016/j.jinf.2009.02.018.
Dengue virus (DV) infections can cause severe life-threatening dengue hemorrhagic fever/dengue shock syndrome (DHF/DSS). However, the mechanism to cause hemorrhage in DV infections remains poorly understood. Thrombomodulin (TM), expressed on the surface of endothelial cells and monocytes, is very important in regulation of coagulation and inflammation. Therefore, the effect of DV on the TM expression was studied in vitro using both endothelial cells and monocytes.
The expression of TM in human endothelial cell line, HMEC-1, monocytic cell line THP-1 and peripheral blood mononuclear cells derived from human blood was increased after DV infection, UV-inactivated DV or recombinant DV envelop protein domain III stimulation as demonstrated by flow cytometry and immunofluorescent staining. Western blot analysis further confirmed only DV but not enterovirus 71 infection of HMEC-1 cells increased TM protein expression. In addition, RT-PCR analysis showed the increase of TM mRNA as well as other protein C activation-related molecules in DV stimulated HMEC-1 in a dose-dependent manner.
These results suggest that DV stimulation of human endothelial cells and monocytes can increase the expression of TM, which may contribute to the anticoagulant properties of cells during DV infection.
登革病毒（DV）感染可导致严重危及生命的登革出血热/登革休克综合征（DHF/DSS）。然而，DV感染导致出血的机制仍知之甚少。血栓调节蛋白（TM）在内皮细胞和单核细胞表面表达，在凝血和炎症调节中非常重要。因此，利用内皮细胞和单核细胞在体外研究了DV对TM表达的影响。
通过流式细胞术和免疫荧光染色证明，DV感染、紫外线灭活的DV或重组DV包膜蛋白结构域III刺激后，人内皮细胞系HMEC-1、单核细胞系THP-1和来源于人血的外周血单个核细胞中TM的表达增加。蛋白质印迹分析进一步证实，只有DV而非肠道病毒71感染HMEC-1细胞会增加TM蛋白表达。此外，逆转录-聚合酶链反应（RT-PCR）分析显示，DV刺激的HMEC-1中TM mRNA以及其他蛋白C激活相关分子呈剂量依赖性增加。
这些结果表明，DV刺激人内皮细胞和单核细胞可增加TM的表达，这可能有助于DV感染期间细胞的抗凝特性。
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