Luplertlop Natthanej, Missé Dorothée
Department of Tropical Hygiene, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand.
Jpn J Infect Dis. 2008 Jul;61(4):298-301.
Dengue hemorrhagic fever and dengue shock syndrome, the major life-threatening outcomes of severe dengue disease, are the consequence of plasma leakage in the vascular areas. We previously demonstrated that dengue virus (DV)-infected dendritic cells (DC) trigger vascular leakage through matrix metalloproteinase (MMP)-9 overproduction, however little is known concerning the consequences of direct infection of macrovascular endothelial cells (MVEC) by DV. In this study, we show that infection of primary human MVEC results in overproduction of MMP-2 and to a lesser extent of MMP-9, leading to enhanced endothelial permeability. This permeability was associated with loss of expression of the vascular endothelium-cadherin cell-cell adhesion. The MMP response to DV infection is strikingly different between DC and MVEC. Therefore, our results demonstrated that endothelial cells are an important target for DV infection, and that DV-induced MMP-2 overproduction by direct infection of endothelial cells may contribute to the pathogenesis of severe dengue infection.
登革出血热和登革休克综合征是严重登革热疾病的主要危及生命的后果，是血管区域血浆渗漏的结果。我们之前证明，登革病毒（DV）感染的树突状细胞（DC）通过基质金属蛋白酶（MMP）-9的过量产生引发血管渗漏，然而，关于DV直接感染大血管内皮细胞（MVEC）的后果知之甚少。在本研究中，我们表明，原代人MVEC的感染导致MMP-2的过量产生以及程度较轻的MMP-9的过量产生，从而导致内皮通透性增强。这种通透性与血管内皮钙黏蛋白细胞间黏附表达的丧失有关。DC和MVEC对DV感染的MMP反应明显不同。因此，我们的结果表明，内皮细胞是DV感染的重要靶点，并且DV通过直接感染内皮细胞诱导MMP-2过量产生可能有助于严重登革热感染的发病机制。
