Dengue Virus Induces Chemokine Release and Degranulation of Human Neutrophils
| Autor: | Mu-Jie Sun, 孫睦傑 |
|---|---|
| Rok vydání: | 2003 |
| Druh dokumentu: | 學位論文 ; thesis |
| Popis: | 91 Dengue viruses (DV) are lipid-enveloped RNA viruses, which are transmitted by the mosquito vectors, Aedes aegypti and Aedes albopictus. DV are the most important flaviviruses in tropical and subtropical countries. Infection with DV may cause mild dengue fever or life threatening diseases such as dengue hemorrhagic fever and dengue shock syndrome. Vascular leakage, hemorrhage, neutropenia and complement activation are the hallmarks of these diseases. Polymorphonuclear leukocytes (PMNs) or neutrophils are critical effectors cells of the innate immune system, which can protect hosts by migrating to inflammatory sites and killing pathogen. However, the role of PMNs in the pathogenesis of DV infection is unclear. In this study, human neutrophils were incubated with DV to understand the effect of DV on the biological activities of neutrophils. Live but not UV inactivated DV (UV-DV) decreased the viability of neutrophils and increased the release of LDH and chemokines such as IL-8, and macrophage inflammatory protein (MIP-1a) from neutrophils. However, the granule enzyme, myeloperoxidase (MPO), was released from both live and UV-DV-stimulated neutrophils. In addition, the levels of IL-8 and MPO in the sera of dengue patients were also increased. Using fluorescent confocal microscopy, we found that DV was phagocytosed into neutrophils and co-localized with FITC-beads in neutrophils. Furthermore, DV-stimulation also increased the expression of CD11b neutrophils and ICAM-1 of HMEC-1 endothelial cell line and increased the binding of neutrophils to endothelial cell. In addition, the signal transduction molecule Toll-like receptor 4 (TLR4) was also increased in DV stimulated neutrophils. Taken together, neutrophils can uptake DV through phagocytosis and kill the virus. In this process, adherence of neutrophils to endothelial cells and necrosis of neutrophils were increased along with the release of chemokines, granule enzymes, and the expression of surface molecule. Therefore neutrophils may play important roles in the innate immune response against DV infection and may also contribute to the pathogenesis of dengue virus infection. |
| Databáze: | Networked Digital Library of Theses & Dissertations |
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