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| DC 欄位 | 值 | 語言 |
|---|---|---|
| dc.contributor.advisor | 伍安怡(Betty A. Wu-hsieh) | |
| dc.contributor.author | Chia-Ching Lin | en |
| dc.contributor.author | 林佳慶 | zh_TW |
| dc.date.accessioned | 2021-06-13T03:17:26Z | - |
| dc.date.available | 2011-08-04 | |
| dc.date.copyright | 2006-08-04 | |
| dc.date.issued | 2006 | |
| dc.date.submitted | 2006-07-30 | |
| dc.identifier.citation | Aggarwal, B. B. (2003). Signalling pathways of the TNF superfamily: a double-edged sword. Nat Rev Immunol 3, 745-756.
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| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/31681 | - |
| dc.description.abstract | 組織胞漿菌是一種寄生在巨噬細胞內之病原性胞內寄生真菌。在受到感染的寄主當中，噬細胞不只是胞漿菌之目的細胞，亦為清除感染之作用細胞並且能夠提供抗原給抗原呈獻細胞。在實驗室之前的研究當中發現到噬細胞在吞入活胞漿菌之後會進行細胞凋亡。樹突狀細胞即可由吞噬死亡之噬細胞當中獲得胞漿菌之抗原，交叉呈獻抗原已活化CD8 T細胞。因此，胞漿菌引發之噬細胞凋亡對於CD8 T 細胞之活化非常地重要。然而，真菌和噬細胞間的交互作用如何引發噬細胞的細胞凋亡仍是一個待解決的課題。本研究的主題當中，就是界定引發噬細胞凋亡的分子。
我首先發現到誘發型一氧化氮合成酵素會在噬細胞感染胞漿菌之後被引發。然而，細胞凋亡率在誘發型一氧化氮合成酵素基因缺陷之噬細胞當中並未降低，而若將噬細胞以活性氧之消除劑N-acetyl- cysteine處理，細胞凋亡率同樣沒有降低的現象，顯示活性氮化物以及活性氧化物皆不參與在噬細胞的凋亡當中。有趣的是，在噬細胞吞入活胞漿菌之後亦會產生腫瘤壞死因子- | zh_TW |
| dc.description.abstract | Histoplasma is a facultative intracellular pathogen of the macrophage. In the infected host, macrophage serves not only as a target cell and an effector cell but also as an antigen donor. Work from our laboratory has shown that macrophages undergo apoptosis after taking up viable Histoplasma yeasts. The dendritic cells take up Histoplasma antigen from dying macrophages cross-prime CD8 T cells. Thus, Histoplasma-induced macrophage apoptosis is important to the activation of CD8 T cells in an infected host. However, it remains to be clarified how the fungus-host cell interaction causes macrophage apoptosis. The focus of the present study was to delineate the molecule(s) that is involved in inducing macrophage apoptosis.
First, I found that inducible nitric oxide synthase (iNOS) was upregulated in macrophages after infection by Histoplasma. However, the apoptosis rate was not reduced in iNOS-deficient macrophages nor in macrophages treated with N-acetyl-cysteine, a reactive oxygen species scavenger, demonstrating neither reactive nitrogen nor oxygen intermediates is involved in macrophage apoptosis. Interestingly, TNF-a production was high in macrophages after uptake of viable Histoplasma. To investigate whether TNF-a is involved in inducing macrophage apoptosis, macrophages from TNF-a-/-, TNFR1-/-, TNFR2-/- and TNFR1-/-R2-/- mice were used. The results showed that in macrophages deficient in TNF-a, TNFR1, TNFR2 or TNFR1R2, the rate of Histoplasma-induced apoptosis was dramatically reduced. Both caspase-8 and pan-caspase inhibitors also significantly reduced macrophage apoptosis. The results of this study demonstrated that production of TNF-a, which through the TNF receptor-transduced signals mediates Histoplasma-induced macrophage apoptosis. | en |
| dc.description.provenance | Made available in DSpace on 2021-06-13T03:17:26Z (GMT). No. of bitstreams: 1 ntu-95-R93449009-1.pdf: 622395 bytes, checksum: 0d65ab89afd5648b0c58c2e77fe8515b (MD5) Previous issue date: 2006 | en |
| dc.description.tableofcontents | Table of Content
Abstract i Abstract (Chinese) iii Chapter I. Introduction Part 1 Histoplasma and host defense 1 Part 2 Pathogen-induced apoptosis 2 Part 3 Cross-presentation 4 Part 4 Rationale to study Histoplasma-induced macrophage apoptosis 5 Chapter II. Materials and Methods Part 1 Experimental procedures 1.1 Mice 6 1.2 Fungus and infection 6 1.3 Culture of primary resident peritoneal macrophage 6 1.4 Total RNA isolation and reverse transcription 7 1.5 Quantitative real-time PCR 8 1.6 TNF-a ELISA assay 8 1.7 Determination of hypoploid cells 9 1.8 TUNEL staining for detection of apoptosis 9 Part 2. Experimental materials 2.1 Complete RPMI-1640 medium 10 2.2 Enriched BHI medium 11 2.3 1X Hank’s balanced solution (HBSS) 11 2.4 Hypotonic DNA staining buffer 11 2.5 10X PBS buffer 11 2.6 ELISA buffer 12 2.7 General materials 12 2.8 Immunological reagents 13 2.9 Sequences primers 14 2.10 Instruments 14 Chapter III. Results Part 1. Histoplasma and macrophage apoptosis 1.1 Macrophages undergo apoptosis after engulfing viable Histoplasma yeast cells 16 Part 2. Histoplasma-induced TNF-a production is the cause of macrophage apoptosis 2.1 Inducible nitric oxide synthase is not involved in Histoplasma-induced macrophage apoptosis 17 2.2 Reactive oxygen species is not involved in Histoplasma-induced macrophage apoptosis 17 2.3 Histoplasma-induced macrophage apoptosis is TNF-a dependent 18 2.4 Signals transduced by both TNFR1 and TNFR2 are important in the induction of apoptosis 19 Part 3. Caspase activation in Histoplasma-induced macrophage apoptosis 3.1 Histoplasma-induced macrophage apoptosis is caspase-dependent 20 Chapter IV. Discussion Part 1. Molecules involved in the Histoplasma-induced macrophage apoptosis. 22 Part 2. Signaling pathways of TNFR1 and TNFR2 that lead to apoptosis. 24 Reference 26 Figures Figure 1. Macrophages undergo apoptosis after ingesting viable Histoplasma yeast cells 32 Figure 2. Histoplasma-induced macrophage apoptosis is not mediated by inducible nitric oxide. 34 Figure 3 Inhibition of ROS production does not reduce Histoplasma-induced macrophage apoptosis.. 36 Figure 4. TNF-a is produced by peritoneal macrophages after engulfing viable Histoplasma. 38 Figure 5. Viable Histoplasma-induced cell death is reduced in the absence of TNF-a 40 Figure 6. Histoplasma-induced macrophage apoptosis is mediated by TNF receptor-transduced signal. 42 Figure 7. Signals transduced by TNFR1 as well as TNFR2 are important in the induction of apoptosis. 44 Figure 8. TNFR1 or TNFR2 macrophages produce same levels of TNF-a as wild type 46 Figure 9.Histoplasma-induced macrophage apoptosis is caspase- dependent. 48 Figure10. Histoplasma-induced macrophage apoptosis is through capsase-8. 50 | |
| dc.language.iso | en | |
| dc.subject | 組織胞漿菌 | zh_TW |
| dc.subject | 細胞凋亡 | zh_TW |
| dc.subject | 噬細胞 | zh_TW |
| dc.subject | 腫瘤壞死因子-a | zh_TW |
| dc.subject | macrophage | en |
| dc.subject | Histoplasma | en |
| dc.subject | TNF-a | en |
| dc.subject | apoptosis | en |
| dc.title | 組織胞漿菌引發巨噬細胞凋亡之研究 | zh_TW |
| dc.title | Study of Histoplasma-Induced Macrophage Apoptosis | en |
| dc.type | Thesis | |
| dc.date.schoolyear | 94-2 | |
| dc.description.degree | 碩士 | |
| dc.contributor.oralexamcommittee | 孔祥智(John T. Kung),廖楓(Fang Liao) | |
| dc.subject.keyword | 組織胞漿菌,噬細胞,細胞凋亡,腫瘤壞死因子-a, | zh_TW |
| dc.subject.keyword | Histoplasma,macrophage,apoptosis,TNF-a, | en |
| dc.relation.page | 51 | |
| dc.rights.note | 有償授權 | |
| dc.date.accepted | 2006-07-30 | |
| 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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