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DC 欄位 | 值 | 語言 |
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dc.contributor.advisor | 伍安怡 | |
dc.contributor.author | Feng-Chiang Wu | en |
dc.contributor.author | 吳豐江 | zh_TW |
dc.date.accessioned | 2021-06-15T06:03:19Z | - |
dc.date.available | 2015-09-09 | |
dc.date.copyright | 2010-09-09 | |
dc.date.issued | 2010 | |
dc.date.submitted | 2010-08-16 | |
dc.identifier.citation | Alvarez, C. P., Lasala, F., Carrillo, J., Muniz, O., Corbi, A. L. And Delgado, R. (2002). C-type lectins DC-SIGN and L-SIGN mediate cellular entry by Ebloa virus in cis and in trans. J Virol 6, 6841-44
Basanta Otero P, Gonzalez Villalonga C, Orbeal Aldama L. Platelet autoantibodies in Dengue hemorrhagic fever. Acta Haematol. 1983;70(2):141-2 Boonpucknavig S, Vuttiviroj O, Bunnag C, Bhamarapravati N, Nimmanitya S. Butthep P, Bunyaratvej A, Bhamarapravati N. Dengue virus and endothelial cell: a related phenomenon to thrombocytopenia and granulocytopenia in dengue hemorrhagic fever. Southeast Asian J Trop Med Public Health. 1993;24 Suppl 1:246-9. Chen, H-C, F-M. Hofman, J-T. Kung, Y-D Lin, and B. A. Wu-Hsieh. (2007). Bothe virus and tumor necrosis factor alpha are critical for endothelium damage in a mouse model of dengue virus-induced hemorrhage. J Viol, 81, 5518-26. Colmenares, M., Puig-Kroger, A., Pello, O. M., Corbi, A. L., and Rivas, L. (2002). Dendritic cell (DC)-specific intercellular adhesion molecule 3 (ICAM-3)-grabbing nonintegrin (DC-SIGN, CD209), a C-type surface lectin in human DCs, is a receptor for Leishmania amasttigotes. J Biol Chem 277, 36766-69. Curtis, B.M., Scharnowske, S., and Watson, A. J. (1992). Sequence and expression of a membrane-associated C-type lectin that exhibits CD4-independent binding of human immunodeficiency virus envelope glycoprotein gp120. Proc Nat Acad Sci U S A 89, 8356-60. Demonstration of dengue antibody complexes on the surface of platelets from patients with dengue hemorrhagic fever. Am J Trop Med Hyg. 1979 Sep;28(5):881-4. Funahara Y, Sumarmo, Shirahata A, Setiabudy-Dharma R. DHF characterized by acute type DIC with increased vascular permeability. Southeast Asian J Trop Med Public Health. 1987 Sep;18(3):346-50 Funahara Y, Sumarmo, Wirawan R. Features of DIC in dengue hemorrhagic fever. Bibl Haematol. 1983;(49):201-11 Gardner, J. P., Durso, R. J., Arrigale, R. R., Donovan, G. P., Maddon, P. J., Dragic, T., and Olson, W. C. (2003). L-SIGN (CD209L) is a liver specific capture receptor for hepatitis C virus. Proc Natl Acad Sci U S A 100, 4498-4503. Geijtenbeek, T. B., Kwon, D. S., Torensma, R., van Vliet, S. J., van Duijnhoven, G. C., Middel, J., Cornelissen, I. L., Nottet, H. S. KewalRamani, V. N., Littman, D. R., et al. (200a). DC-SIGN, a dendretic cell-specific HIV-1-biding protein that enhances trans-infection of T cells. Cell 100, 587-597. Geijtenbeek, T. B., Torensma, R., van Vliet, S. J., van Duijnhoven, G. C., Adema, G. J., van Kooyk, Y., and Figdor, C. G. (2000b). Identification of DC-SIGN, a novel dendrtic cell-specific ICAM-3 receptor that supports primary immune responese. Cell 100, 575-585. Geijtenbeek, T. B., van Duijnhoven, G. C.,van Vliet, S. J., Drieger, E., Vriend, G., Figdor, C. G., and van Kooyk, Y. (2002) Idetification of different binding site in the dendritic cell-specific receptor DC-SIGN for intercellular adhesion molecule 3 and HIV-1. J Biol Chem 277, 11314-11320. Geijtenbeek, T. B., van Vliet, S. J., Koppel, E. A., Sanchez-Hernandez, M., Van denbroucke-Grauls, C. M., Appelmelk, B., and van Kooyk, Y. (2003). Mycobacteria target DC-SIGN to suppress dendritic cell function. J Exp Med 197, 7-17. Ghosh K, Gangodkar S, Jain P, Shetty S, Ramjee S, Poddar P, Basu A. Imaging the interaction between dengue 2 virus and human blood platelets using atomic force and electron microscopy. J Electron Microsc (Tokyo). 2008 Jun;57(3):113-8. Epub 2008 May 8. Gringhuis SI, Deng Dunnen J, Litjens M, van het Hof B, van Kooyk Y, Geijtenbeek TBH. (2007). C-type lection DC-SIGN modulates toll-like receptor signaling via Raf-1 kinase-dependent acetylation of transcription factor NF-kappa B. Immunity 26, 605. Guaman, M. G., and Kouri, G. (2002). Dengue: an update. Lancet Infect Dis 2, 33-42. Halary, F., Amara, A., Lortat-Jacob, H., Messerle, M., Delaunay, T., Houlesm, C., Fieschi, F., Arenzana-Seisdedos, F., Moreau, J. F., and Dechanet-Merville, J. (2002). Human cytomegalovirus binding to DC-SIGN is required for dendritic cell infection and target cell trans-infection. Immunity 17, 653-664. Jeroen den Dunnen, Sonja I. Gringhuis, Teunis B. H. Geijtenbeek. (2009). Innate signaling by the C-type lectin DC-SIGN dictates immune responses. Cancer Immunol Immunother. 58, 1149-1157 Krishnamurti C, Peat RA, Cutting MA, Rothwell SW. Platelet adhesion to dengue-2 virus-infected endothelial cells. Am J Trop Med Hyg. 2002 Apr;66(4):435-41. Kuhn, R. J., Zhang, W., Rossmann, M. G., Pletnev, S. V., Corver, J., Lenches, E., Jones, C. T., Mukhopadhyay, S., Chipman, P. R., Strauss, E. G., et al (2002). Structure of dengue virus: implications for favivirus organization, maturation, and fusion. Cell 108, 717-725. Mairuhu, A. T., Wagenaar, J., Brandjes, D. P., and van Gorp, E. C. (2004). Dengue: an arthropod-bourne disease of global importance. Eur J Clin Microbiol Infect Dis 23, 425-433. Navarro-Sanchez, E., Altmeyer, R., Amara, A., Schwartz, O., Fieschi, F., Virelizier, J. L., Arenzana-Seisdedos, F., and Despres, P. (2003). Dendritic-cell-specific ICAM3-grabbing non-integrin is essential for the productive infection of human dendritic cells by mosquito-cell-derived dengue viruses. EMBO Rep 4, 723-728. Noisakran S, Gibbons RV, Songprakhon P, Jairungsri A, Ajariyakhajorn C, Nisalak A, Jarman RG, Malasit P, Chokephaibulkit K, Perng GC. Detection of dengue virus in platelets isolated from dengue patients. Southeast Asian J Trop Med Public Health. 2009 Mar;40(2):253-62. Oishi K, Inoue S, Cinco MT, Dimaano EM, Alera MT, Alfon JA, Abanes F, Cruz DJ, Matias RR, Matsuura H, Hasebe F, Tanimura S, Kumatori A, Morita K, Natividad FF, Nagatake T. Correlation between increased platelet-associated IgG and thrombocytopenia in secondary dengue virus infections. J Med Virol. 2003 Oct;71(2):259-64. Phanichyakarn P, Israngkura PB, Krisarin C, Pongpanich B, Dhanamitta S, Valyasevi A. Studies on dengue hemorrhagic fever. IV. Fluorescence staining of the immune complexes on platelets. J Med Assoc Thai. 1977 Jul;60(7):307-11 Rigau-Perez, J. G., Clark, G. G., Gubler, D. J., Reiter, P., Sanders, E. J., and Vorndam, A. V. (1980). Isolation of dengue viruses from peripheral blood leukocytes of patients with hemorrhagic fever. J Infect Dis 141, 1-6. Saito M, Oishi K, Inoue S, Dimaano EM, Alera MT, Robles AM, Estrella BD Jr, Kumatori A, Moji K, Alonzo MT, Buerano CC, Matias RR, Morita K, Natividad FF, Nagatake T. Association of increased platelet-associated immunoglobulins with thrombocytopenia and the severity of disease in secondary dengue virus infections. Clin Exp Immunol. 2004 Nov;138(2):299-303. Srichaikul T, Nimmanitaya S, Artchararit N, Siriasawakul T, Sungpeuk P. (1997) Fibrinogen metabolism and disseminated intravascular coagulation in dengue hemorrhagic fever. Am J Trop Med Hyg 26(3):525-32. Srichaikul T, Nimmannitya S, Sripaisarn T, Kamolsilpa M, Pulgate C. Platelet function during the acute phase of dengue hemorrhagic fever. Southeast Asian J Trop Med Public Health Sumaromo, Wulur, H., Jahja, E., Gubler, D. J., Suharyono, W., and Sorensen, K. (1983). Clincal observations on virologically confirmed fatal dengue infection in Jakarta, Indonesia. Bull Woirld Health Organ 61, 693-701. Sun DS, King CC, Huang HS, Shih YL, Lee CC, Tsai WJ, Yu CC, Chang HH. Antiplatelet autoantibodies elicited by dengue virus non-structural protein 1 cause thrombocytopenia and mortality in mice. J Thromb Haemost. 2007 Nov;5(11):2291-9. Ui-Soon Khoo, Kelvin Y. K. Chan, Vera S. F. Chan, C. L. Steve Lin. (2008). DC-SIGN and L-SIGN: the SIGNS for infection. J Mol Med 86, 861-874. Van Kooyk, Y., and Geijtenbeek, T. B. (2002). A novel adhesion pathway that regulate dendritic cell trafficking and T cell interactions. Immunol Rev 186, 47-56. Wang S, He R, Patarapotikul J, Innis BL, Anderson R. Antibody-enhanced binding of dengue-2 virus to human platelets. Virology. 1995 Oct 20;213(1):254-7. Wellbrock C, Karasarides M, Marais R. (2004). The RAF proteins take centre stage. Nat Rev Mol Cell Biol 5, 875. Y-T Yen, H-C Chen, Y-D Lin, C-C Shen, and betty A. Wu-Hsieh. (2008). Enhancement by tumore cecrosis factor alpha of dengue virus-induced endothelial cell prodution of reactive nitrogen and oxygen species is key to hemorrhage development. J Virol. 24, 12312-12324. | |
dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/47505 | - |
dc.description.abstract | 登革是世界上散播最廣的感染性疾病之一,已經引起很大的公共衛生問題。許多流行病學上的假設都希望能夠解釋嚴重登革疾病的發生。然而,目前並沒有適當的動物模式能測試這些假設。
有報告指出DC-SIGN為登革病毒的受體。本研究室先前以基因轉殖方式在C57BL/6小鼠背景製造出DC-SIGN基因轉殖小鼠。此轉殖鼠在大部份的器官皆表現DC-SIGN的訊息核糖核酸,並且單核血球細胞、腹腔巨噬細胞、及脾臟巨噬細胞在細胞膜上都表現DC-SIGN蛋白質。相較於野生型小鼠的腹腔巨噬細胞,轉殖鼠的腹腔巨噬細胞在體外受到登革病毒的刺激後會產生較高的α腫瘤壞死因子。利用共軛焦顯微鏡,我發現轉殖鼠的腹腔巨噬細胞於受到登革病毒感染後六小時,DC-SIGN和病毒抗原朝細胞的同一端移動,並於第十二小時開始出現抗原交疊的情形。此外,轉殖鼠的腹腔巨噬細胞於受到登革病毒感染後形態變化的時間點均較野生型的腹腔巨噬細胞晚。至於其中的細胞學機制尚待研究。 進一步觀察DC-SIGN所調控的細胞訊息傳導,我比較DC-SIGN轉殖的小鼠B細胞株M12-DC-SIGN和野生型M12,發現經登革病毒感染後M12-DC-SIGN比野生型的M12表現較低量的Erk、p38、活化的Erk和活化的p38。可見登革病毒透過DC-SIGN所引起的細胞訊息傳遞可能不增加MAPK的磷酸化。 為了測試流行病學上感染密集度會影響疾病嚴重程度的假設,我利用DC-SIGN基因轉殖小鼠來研究2002高雄登革大流行時臨床收集的登革病毒株誘發出血的潛力。這些病毒株依病患居住區屬於高或低感染密集區及病人疾病之診斷結果為登革熱或登革出血熱分類。我發現,自高感染密集區病患分離出來的病毒較低感染密集區病患分離出來的病毒引發轉殖鼠較高的出血比率以及較嚴重的出血現象。此外,於同一地區,分離自登革出血熱病患的病毒較分離自登革熱病患的病毒更易引起高出血比率和嚴重的出血現象。相較於分離自登革熱病人的病毒,分離自登革出血熱病患的病毒能引發轉殖鼠的腹腔巨噬細胞產生較高量的α腫瘤壞死因子。進一步觀察經感染後小鼠出血和無出血的皮膚組織,發現出血的皮膚組織內確實也有較高量α腫瘤壞死因子。 這是首次利用人類基因轉殖小鼠來研究臨床分離的登革病毒誘發出血的潛力。研究結果顯示高密集區的病毒較易引發高出血率和嚴重的出血現象,而且分離自登革出血熱病人的病毒較易引發高出血率和嚴重的出血現象。同時,分離自登革出血熱病人的病毒也能夠引發轉殖鼠的腹腔巨噬細胞產生較高量的α腫瘤壞死因子,這可能是這些病毒株較易引發出血的原因之ㄧ。 | zh_TW |
dc.description.provenance | Made available in DSpace on 2021-06-15T06:03:19Z (GMT). No. of bitstreams: 1 ntu-99-R97449004-1.pdf: 4419764 bytes, checksum: db54c2672be4243741a8f0feaa7654c5 (MD5) Previous issue date: 2010 | en |
dc.description.tableofcontents | Abstract………………………………………………………………………………..i
Abstract (Chinese)…………………………………………………………………...iv Table of Contents…………………………………………………………………….vi List of Figures………………………………………………………………………..ix Chapter I. Introduction………………………………………………………….-1- 1.1 Dengue viruses and diseases………………………………………….…….-1- 1.2 Mouse models to study the pathogenesis and immune response against dengue virus………………………………………………………………...-2- 1.3 Dengue virus receptors…………………………………………………......-4- 1.4 DC-SIGN and DC-SIGN transgenic mouse……………………………......-5- 1.5 DC-SIGN-mediated cell signaling………………………….........................-8- 1.6 Dengue outbreak in Kaohsiung at 2002…………………………………….-9- Chapter II. Materials and Methods…………………………………………...-11- 2.1 Materials…………………………………………………………………..-11- Mice….……………………………………………...…………………...-11- Virus….……………………………………………...…………………..-11- Antibodies………………………………………...…………………….-12- Solutions……………….………………………...……………………...-14- Chemicals, reagents and equipments…………....…….………………...-19- Primers………………………………...………….……………………..-22- 2.2 Methods………………………………………………………………...-23- Genotyping of DC-SIGN transgene Infection of mice with dengue virus……………………………………-23- Infection of macrophages with dengue virus………………...…………-23- Quantification of tissue DC-SIGN gene expression……...………….…-24- Confocol microscopy………………………………………….….….…-26- Skin cytokine extraction…………………………………….……….…-27- TNF-αproduction after infection of macrophage…………………..…-27- ELISA……………………………………………………………….…-27- Western blotting……………………………………………………..…-28- Surface staining of macrophage………………………………….….…-29- Chapter III. Results…………………………………………………………...-31- 3.1 To investigate the mechanism of hemorrhage development induced by dengue viruses in a DC-SIGN transgenic mouse model……………….…-31- 3.1.1 DC-SIGN expression in transgenic mouse and macrophages………-31- 3.1.2 Interaction between DC-SIGN and dengue viral antigen…………...-32- 3.1.3 Dengue virus-induced TNF-αproduction by transgenic mouse peritoneal macrophages………………………………………..…...-33- 3.1.4 Dengue virus-induced downstream signaling of DC-SIGN………..-34- 3.2 To test epidemiological findings concerning dengue hemorrhage in DC-SIGN transgenic mouse model…………………………………………………..-35- 3.2.1 Hemorrhage induction potentials of different epidemiological isolates……………………………………………………...………-35- 3.2.2 The role of TNF-αin induction of hemorrhage……………...……..-37- Chapter IV. Discussion 4.1 DC-SIGN transgenic mice and dengue hemorrhage mouse model……….-39- 4.2 DC-SIGN interaction with dengue virus in macrophages from transgenic mice…………………………………………………………....-41- 4.3 The role of TNF-αin hemorrhage development in transgenic model system…………………………………………………………………......-42- 4.4 Downstream signaling of DC-SIGN………………………………………-43- 4.5 Applying DC-SIGN transgenic mouse model to study epidemiological isolates…………………………………………………………………….-44- 4.6 Summary…………………………………………………………………..-46- Reference……………………………………………………………………….-47- Tables and Figures……………………………………………………………..-53- Chapter V. Appendix…………………………………………………………..-72- Results…………………………………………………………….…………..-72- Tables and Figures……………………………………………..….…………..-75- | |
dc.language.iso | en | |
dc.title | 探討登革病毒於人類DC-SIGN基因轉殖小鼠模式中引發出血的機制並探究2002年高雄第二型登革病毒的流行愈趨嚴重之出血潛力 | zh_TW |
dc.title | Investigation on the underlying mechanisms of hemorrhage induced by dengue viruses in DC-SIGN transgenic mouse model and testing for the increasing epidemic severity and hemorrhagic potential of dengue serotype 2 viruses isolated from the 2002 epidemic in Kaohsiung | en |
dc.type | Thesis | |
dc.date.schoolyear | 98-2 | |
dc.description.degree | 碩士 | |
dc.contributor.oralexamcommittee | 顧家綺,金傳春,張雯 | |
dc.subject.keyword | 登革,登革熱,登革出血熱,腫瘤壞死因子,小鼠模式,DC-SIGN;2002高雄登革爆發, | zh_TW |
dc.subject.keyword | dengue,dengue fever,dengue hemorrhagic fever,TNF,mouse model,2002 Kaohsiung dengue outbreak, | en |
dc.relation.page | 85 | |
dc.rights.note | 有償授權 | |
dc.date.accepted | 2010-08-16 | |
dc.contributor.author-college | 醫學院 | zh_TW |
dc.contributor.author-dept | 免疫學研究所 | zh_TW |
顯示於系所單位: | 免疫學研究所 |
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