Studies on the Pathological Role of Antibodies Against Dengue Virus Nonstructural Protein 1 Both in Vitro and in Vivo
碩士 === 國立成功大學 === 微生物暨免疫學研究所 === 90 === 英文摘要 Dengue virus (DV), the member of Flaviviridae, are transmitted by Aedes aegypti or Aedes albopictus. In clinical, patients with DV infection show a wide range of disease severity from mild febrile illness as dengue fever to life-threatening den...
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ndltd-TW-090NCKU03800162016-06-27T16:08:45Z http://ndltd.ncl.edu.tw/handle/87731074301395917480 Studies on the Pathological Role of Antibodies Against Dengue Virus Nonstructural Protein 1 Both in Vitro and in Vivo 抗登革病毒非結構性蛋白1抗體在體外及體內模式上病理角色之研究 Shu-Chen Chiu 邱淑貞 碩士 國立成功大學 微生物暨免疫學研究所 90 英文摘要 Dengue virus (DV), the member of Flaviviridae, are transmitted by Aedes aegypti or Aedes albopictus. In clinical, patients with DV infection show a wide range of disease severity from mild febrile illness as dengue fever to life-threatening dengue hemorrhagic fever and dengue shock syndrome (DHF/DSS). Thrombocytopenia, vascular leakage, and hemorrhagic syndrome are the hallmarks of the DHF/DSS. However, the pathogenesis of DHF/DSS is poorly understood. Previous studies in our laboratory showed the endothelial cell dysfunction caused by antibodies (Abs) against DV nonstructural protein 1 (NS1). Anti-NS1 Abs from dengue patients cross-reacted with endothelial cells and caused endothelial cell apoptosis. In this study, anti-NS1 Abs were generated in mice and their effects on endothelial cells (HMEC-1) were examined. The cross-reactivity of anti-NS1 Abs with HMEC-1 cells was detected by immunostaining. The binding activity of anti-NS1 Abs was also observed in vascular endothelium of mouse vessel ex vivo. Western blot analysis demonstrated that proteins with molecular weights of approximately 95-, 130- and 150-kDa could be detected following the hybridization of anti-NS1 Abs with endothelial cell extract membrane fractions. Anti-NS1-induced HMEC-1 apoptosis could be observed when Abs were incubated with cells for 1 h, followed by 12 or 24 h further cultivation. The cytokine and chemokine production after anti-NS1 stimulation was also examined. Results showed that the expression of IL-6、IL-8 and MCP-1, but not RANTES, in endothelial cells increased after treatment with anti-NS1 Abs. Furthermore, we found that expression of ICAM-1 was induced and the adhesion ability of PBMC was upregulated after anti-NS1 stimulation. In the animal studies, the levels of AST and ALT in mouse sera increased after passive administration of anti-NS1 Abs. The pathological effects of anti-NS1 Abs in mouse liver revealed macrophages infiltratration and some cells undergoing apoptosis. Taken together, these findings may provide the evidence on the pathological role of anti-NS1 Abs in DV infection. Yee-Shin Lin 林以行 2002 學位論文 ; thesis 89 zh-TW |
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碩士 === 國立成功大學 === 微生物暨免疫學研究所 === 90 === 英文摘要
Dengue virus (DV), the member of Flaviviridae, are transmitted by Aedes aegypti or Aedes albopictus. In clinical, patients with DV infection show a wide range of disease severity from mild febrile illness as dengue fever to life-threatening dengue hemorrhagic fever and dengue shock syndrome (DHF/DSS). Thrombocytopenia, vascular leakage, and hemorrhagic syndrome are the hallmarks of the DHF/DSS. However, the pathogenesis of DHF/DSS is poorly understood. Previous studies in our laboratory showed the endothelial cell dysfunction caused by antibodies (Abs) against DV nonstructural protein 1 (NS1). Anti-NS1 Abs from dengue patients cross-reacted with endothelial cells and caused endothelial cell apoptosis. In this study, anti-NS1 Abs were generated in mice and their effects on endothelial cells (HMEC-1) were examined. The cross-reactivity of anti-NS1 Abs with HMEC-1 cells was detected by immunostaining. The binding activity of anti-NS1 Abs was also observed in vascular endothelium of mouse vessel ex vivo. Western blot analysis demonstrated that proteins with molecular weights of approximately 95-, 130- and 150-kDa could be detected following the hybridization of anti-NS1 Abs with endothelial cell extract membrane fractions. Anti-NS1-induced HMEC-1 apoptosis could be observed when Abs were incubated with cells for 1 h, followed by 12 or 24 h further cultivation. The cytokine and chemokine production after anti-NS1 stimulation was also examined. Results showed that the expression of IL-6、IL-8 and MCP-1, but not RANTES, in endothelial cells increased after treatment with anti-NS1 Abs. Furthermore, we found that expression of ICAM-1 was induced and the adhesion ability of PBMC was upregulated after anti-NS1 stimulation. In the animal studies, the levels of AST and ALT in mouse sera increased after passive administration of anti-NS1 Abs. The pathological effects of anti-NS1 Abs in mouse liver revealed macrophages infiltratration and some cells undergoing apoptosis. Taken together, these findings may provide the evidence on the pathological role of anti-NS1 Abs in DV infection.
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author2 |
Yee-Shin Lin |
author_facet |
Yee-Shin Lin Shu-Chen Chiu 邱淑貞 |
author |
Shu-Chen Chiu 邱淑貞 |
spellingShingle |
Shu-Chen Chiu 邱淑貞 Studies on the Pathological Role of Antibodies Against Dengue Virus Nonstructural Protein 1 Both in Vitro and in Vivo |
author_sort |
Shu-Chen Chiu |
title |
Studies on the Pathological Role of Antibodies Against Dengue Virus Nonstructural Protein 1 Both in Vitro and in Vivo |
title_short |
Studies on the Pathological Role of Antibodies Against Dengue Virus Nonstructural Protein 1 Both in Vitro and in Vivo |
title_full |
Studies on the Pathological Role of Antibodies Against Dengue Virus Nonstructural Protein 1 Both in Vitro and in Vivo |
title_fullStr |
Studies on the Pathological Role of Antibodies Against Dengue Virus Nonstructural Protein 1 Both in Vitro and in Vivo |
title_full_unstemmed |
Studies on the Pathological Role of Antibodies Against Dengue Virus Nonstructural Protein 1 Both in Vitro and in Vivo |
title_sort |
studies on the pathological role of antibodies against dengue virus nonstructural protein 1 both in vitro and in vivo |
publishDate |
2002 |
url |
http://ndltd.ncl.edu.tw/handle/87731074301395917480 |
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