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DC 欄位 | 值 | 語言 |
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dc.contributor.advisor | 詹東榮(Tong-Rong Jan) | |
dc.contributor.author | Chien-Chang Shen | en |
dc.contributor.author | 沈建璋 | zh_TW |
dc.date.accessioned | 2021-06-07T17:49:53Z | - |
dc.date.copyright | 2013-02-16 | |
dc.date.issued | 2013 | |
dc.date.submitted | 2013-01-28 | |
dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/15677 | - |
dc.description.abstract | 氧化鐵奈米粒子是臨床上使用的核磁共振造影的對比劑。文獻指出氧化鐵奈米粒子會影響免疫細胞的功能,如巨噬細胞、T細胞及樹突細胞等,動物實驗顯示氣管內給予氧化鐵奈米粒子會導致肺臟發炎反應。本研究主旨在探討氧化鐵奈米粒子對抗原專一性T細胞免疫反應的影響。結果顯示靜脈注射一劑氧化鐵奈米粒子 (10-60 mg Fe/kg) 會降低卵白蛋白 (ovalbumin) 致敏小鼠血清中抗原專一性抗體濃度及抑制T細胞的功能。將卵白蛋白致敏的脾臟細胞 (splenocyte) 於離體培養條件下直接暴露氧化鐵奈米粒子 (1-100 μg Fe/mL),其存活率及介白素-2 (interleukin-2, IL-2) 及介白素-4 (IL-4) 的表現未受影響,但伽馬干擾素 (interferon-γ) 的製造及細胞內谷胱甘肽 (glutathione)的含量受到抑制,且呈現濃度相關性,這些抑制反應可被谷胱甘肽前驅物乙醯基半胱氨酸 (N-acetyl-L-cysteine) 所減緩。此外,靜脈注射一劑氧化鐵奈米粒子 (0.2-10 mg Fe/kg) 亦可抑制遲發性過敏反應,包括腳掌腫脹程度、發炎部位巨嗜細胞及T細胞的浸潤、與介白素-6 (IL-6)、伽馬干擾素及腫瘤壞死因子-α (tumor necrosis factor-α) 的表現量,且脾臟CD11b+細胞之吞噬功能亦有被抑制的情形。上述結果指出氧化鐵奈米粒子可抑制抗原專一性T細胞免疫反應,且藉由抑制第一輔助型T細胞及巨噬細胞的功能,而達到抑制遲發性過敏反應的作用。本論文的結果可提供氧化鐵奈米粒子對抗原專一性體液性及細胞性免疫反應作用之參考依據。 | zh_TW |
dc.description.abstract | Iron oxide nanoparticles have been used in clinical as a contrasting agent to enhance magnetic resonance imaging. Accumulating evidence indicates that iron oxide nanoparticles modulate the functionality of macrophages, T cells and dendritic cells. Animal studies show that intratracheal administration of iron oxide nanoparticles causes lung inflammation. The objective of the present study is to investigate the potential immune modulatory effect of iron oxide nanoparticles on antigen-specific T cell immunity. The results showed that a single intravenous injection of iron oxide nanoparticles (10-60 mg Fe/kg) attenuated the serum production of antigen-specific antibodies and T cell reactivity in ovalbumin (OVA)-sensitized mice. Direct exposure of OVA-primed splenocytes to iron oxide nanoparticles (1-100 μg Fe/mL) did not affect cell viability and the production of interleukin (IL)-2 and IL-4, whereas the production of interferon (IFN)-γ and intracellular glutathione, was markedly suppressed by iron oxide nanoparticles in a concentration-dependent manner. The effects of iron oxide nanoparticles on IFN-γ and glutathione were attenuated by the presence of N-acetyl-L-cysteine, a precursor of glutathione. Furthermore, intravenous administration of iron oxide nanoparticles (0.2-10 mg Fe/kg), in a dose-dependent fashion, significantly suppressed inflammatory responses associated with delayed-type hypersensitivity (DTH), including the footpad swelling, the infiltration of T cells and macrophages, and the expression of IFN-γ, IL-6 and tumor necrosis factor-α in the inflammatory region. A suppressive effect on the phagocytic activity of splenic CD11b+ cells was also observed. Taken together, the present study demonstrated that iron oxide nanoparticles markedly attenuated antigen-specific T cell immunity and the inhibition of DTH reactions could be mediated by suppressing the functional activity of T helper 1 cells and macrophages. These results provide critical insights into the potential health impact of iron oxide nanoparticles on both humoral and cell-mediated immunity. | en |
dc.description.provenance | Made available in DSpace on 2021-06-07T17:49:53Z (GMT). No. of bitstreams: 1 ntu-102-D98629001-1.pdf: 20192927 bytes, checksum: f8079239c439fcae5ecfe5d601922488 (MD5) Previous issue date: 2013 | en |
dc.description.tableofcontents | 口試委員審定書 I
致謝 II 中文摘要 III Abstract IV Content VI Figures VIII Tables IX Abbreviations X Chapter 1 Introduction 1 1.1 Background of nanoparticles 1 1.2 Nanotoxicology 1 1.3 Immunological impacts of nanoparticles 4 1.4 Background of iron oxide nanoparticles 7 1.5 Toxicity of iron oxide nanoparticles 8 1.6 Immunomodulatory effects of iron oxide nanoparticles 12 1.7 Mechanisms and factors associated with nanotoxicity 13 1.8 T cell-mediated immunity 17 1.9 Delayed-type hypersensitivity reactions 18 1.10 Objective of the study 19 Chapter 2 Materials and methods 22 2.1 Chemicals and reagents 22 2.2 Animals 24 2.3 In vivo study protocols 24 2.3.1 Animal experiment protocol of iron oxide nanoparticle administration and OVA sensitization 24 2.3.2 Animal experiment protocol of delayed-type hypersensitivity 27 2.4 In vitro study protocol 29 2.5 Splenocyte culture 29 2.6 Measurement of splenocyte viability 29 2.7 Measurement of cytokines by ELISA 30 2.8 Measurement of OVA-specific IgG by ELISA 31 2.9 Flow cytometric analysis of splenocyte cellularity 32 2.10 Flow cytometric analysis of intracellular glutathione 32 2.11 Reactive oxygen species measurement 32 2.12 Histological analysis and immunohistochemical staining of footpads 33 2.13 Measurement of the phagocytic activity of splenic CD11b+ cells 33 2.14 Statistical analysis 34 Chapter 3 Results 35 3.1 Iron oxide nanoparticle administration attenuated antigen-specific humoral immunity and T cell reactivity in BALB/c mice 35 3.1.1 Iron oxide nanoparticles reduced serum levels of antigen-specific antibody 35 3.1.2 Iron oxide nanoparticles suppressed antigen-induced T cell reactivity 37 3.2 Direct effects of iron oxide nanoparticles on the functionality of OVA-primed splenocytes 41 3.2.1 No effect of direct exposure to iron oxide nanoparticles on splenocyte viability 41 3.2.2 Differential effects of iron oxide nanoparticles on the expression of antigen-specific cytokines by OVA-primed splenocytes 43 3.2.3 Attenuation of iron oxide nanoparticle-mediated inhibition of IFN-γ by thiol, but not nonthiol, antioxidants 46 3.2.4 Diminishment of intracellular glutathione by iron oxide nanoparticles 49 3.3 Iron oxide nanoparticles suppressed Th1 cell-mediated immunity in murine model of delayed-type hypersensitivity 52 3.3.1 Administration of iron oxide nanoparticles suppressed delayed-type hypersensitivity reactions 52 3.3.2 Differential effects of iron oxide nanoparticles on T cell functionality 62 3.3.3 Effects of iron oxide nanoparticles on phagocytic activity of CD11b+ splenocytes. 65 Chapter 4 Discussion 68 Chapter 5 Future perspective 77 Reference 79 | |
dc.language.iso | en | |
dc.title | 氧化鐵奈米粒子對抗原專一性T細胞免疫及遲發性過敏反應的影響 | zh_TW |
dc.title | The effects of iron oxide nanoparticles on antigen-specific T cell immunity and delayed-type hypersensitivity | en |
dc.type | Thesis | |
dc.date.schoolyear | 101-1 | |
dc.description.degree | 博士 | |
dc.contributor.oralexamcommittee | 周晉澄(Chin-Cheng Chou),龐飛(Victor Fei Pang),陳炯東(Chiung-Tong Chen),廖俊旺(Jiunn-Wang Liao),梁弘人(Hong-Jen Liang) | |
dc.subject.keyword | 介白素,抗原專一性,遲發性過敏反應,氧化鐵奈米粒子,T細胞, | zh_TW |
dc.subject.keyword | antigen-specific,cytokine,delayed-type hypersensitivity,iron oxide nanoparticle,T cell, | en |
dc.relation.page | 98 | |
dc.rights.note | 未授權 | |
dc.date.accepted | 2013-01-28 | |
dc.contributor.author-college | 獸醫專業學院 | zh_TW |
dc.contributor.author-dept | 獸醫學研究所 | zh_TW |
顯示於系所單位: | 獸醫學系 |
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