Reactive Nitrogen and Oxygen Species are Critical to Endothelium Damage in Dengue Hemorrhage Mouse Model
Date Issued
2007
Date
2007
Author(s)
Lin, Yang-Ding
DOI
en-US
Abstract
Dengue hemorrhagic fever and dengue shock syndrome (DHF/DSS) are severe dengue disease. However, the underlying pathogenic mechanisms involved in severe dengue disease remain unclear. Recent studies demonstrated that endothelial cells (ECs) are targeted by dengue virus and vascular disorder may occur. Results from study of dengue hemorrhage mouse model provided evidence to support the possibility that EC damage is key to the pathogenesis of DHF. In the present study, immunocompetent C57BL/6 mice were inoculated with different titers of DENV sertotype 2 strain 16681 through the intradermal route. While 81.8%, 54.5%, and 36.3% of the mice receiving 2 × 109, 4 × 108, and 4 × 107 PFU DV developed hemorrhage, none of those given 4 × 106 PFU did at 3 days after infection. Flow cytometric analysis showed that mice that developed hemorrhage had numbers of circulating endothelial cells (CECs) in the peripheral blood. Furthermore, hemorrhage was accompanied by significant reduction of platelet counts. Immunofluorescence staining revealed that ECs express iNOS and nitrotyrosine in the endothelium of hemorrhage tissues, suggesting oxidative stress created by the production of high output nitric oxide and reactive oxygen species is involved in endothelium damage. To test whether nitric oxide and reactive oxygen species participate in DV-induced hemorrhage, iNOS-/- mice were treated with NADPH oxidase inhibitor. The results showed that iNOS deficiency or inhibition of ROS production reduced the percentage of mice that developed hemorrhage from 77.8 % to 33.3 and 28.6 %, respectively. Combination of iNOS deficiency and oxidase inhibitor had additive effect to reduce the severity of hemorrhage as well as the percentage of mice that developed hemorrhage. Taken together, the results of the present study demonstrate that both reactive nitrogen and oxygen species are responsible for the pathogenesis of DENV-induced hemorrhage in the mouse model. Additionally, this study also showed that high numbers of CECs and low platelet counts can be used as indicators for hemorrhage development.
Subjects
小鼠模式
活性氮
活性氧
血管內皮
Mouse Model
Reactive Nitrogen Species
Reactive Oxygen Species
Endothelium Damage
SDGs
Type
other
File(s)![Thumbnail Image]()
Loading...
Name
ntu-96-R94449006-1.pdf
Size
23.31 KB
Format
Adobe PDF
Checksum
(MD5):c3d3329d769d8189f84143fe38faf84a