臺灣博碩士論文加值系統

樹狀突細胞 ( Dendritic cell；DC ) 和肺泡巨噬細胞 ( Alveolar macrophage；AM ) 為重要的抗原呈獻細胞，其上的pattern recognition receptors 如類鐸接受體 ( Toll-like receptor；TLR ) 與抗原分子結合後活化DC和AM並分泌細胞激素 ( Cytokines )，這些細胞激素可誘導T細胞發展為適當的作用細胞。本實驗以豬生殖與呼吸綜合症病毒 ( Porcine reproductive and respiratory syndrome virus；PRRSV ) 感染豬樹狀突細胞及豬肺泡巨噬細胞，於感染後不同時間萃取其mRNA，以RT-PCR或 real-time PCR測定TLRs，促發炎細胞素，趨化激素，Th1和Th2細胞激素mRNA含量。結果顯示，PRRSV感染後6小時DC和AM之TLRs mRNA表現量呈現短暫下降但未達顯著水準 ( P < 0.05 )；受PRRSV感染之DC 其IL-1β、IL-8、IL-12p40、TNF-α及MCP-1的mRNA表現量呈現隨感染時間之增加而上升但只有IL-1β及TNF-α達顯著水準 ( P < 0.05 )，AM受感染後其IL-1β、TNF-α、MCP-1及IFN-γ的mRNA表現量呈現隨感染時間之增加而上升但未達顯著水準 ( P < 0.05 )。 real-time PCR與RT-PCR測定的結果除了PRRSV感染AM之IL-10和TLR3 mRNA之定量兩種方法所得結果之相關係數 ( r = 0.12和r = 0.06 ) 較低外，其它結果成高度相關，其相關係數達到0.62-0.8。

Dendritic cell ( DC ) and Alveolar macrophage ( AM ) are important antigen-presenting cells. The binding between pattern recognition receptors such as Toll-like receptors ( TLR ) on DC and AM and pathogen-associated molecular pattern resulted in the secretion of various cytokines which the modulate T cell responses of appropriate effector phenotypes accordingly. In this study, porcine immature DC ( imDC ) and AM were infected with porcine reproductive and respiratory syndrome virus ( PRRSV ). The mRNA expressions of TLRs, pro-inflammatory cytokines, chemokines, T help 1 ( Th1 ) and Th2 cytokines were detected by reverse transcription-polymerase chain reaction ( RT-PCR ) and real-time PCR from cells at various periods of times after infection. Results showed that the mRNA expression of TLRs in DCs and AMs had a transient and insignificant decrease 6 hours after the infection. Thereafter, the mRNA expression of IL-1β, IL-8, IL-12p40, TNF-α and MCP-1 in DCs were increased as the infection intervals increased but only IL-1β and TNF-α had reached significant ( P < 0.05 ) levels. An insignificant increase of mRNA expression of IL-1β, TNF-α, MCP-1 and IFN-γ in AM were also observed as the infection intervals increased. A high correlation ( r = 0.62-0.8 ) between the results measured by RT-PCR and real-time PCR was obtained except for the results of IL-10 and TLR3 mRNA which had a low correlation coefficient of 0.12 and 0.06.

中文摘要 ...…………………………………………………………….…...I
英文摘要 …...…………………………………………………………..…..II
誌 謝 ……………………………………………………………..…….IV
目 錄 ……………………………………………………………..…….V
圖表目錄 ………………………………………………………………..….VIII
第 1 章 前 言 …………………………………………………..…...1
第 2 章 文獻回顧 …………………………………………………….....4
2. 1 肺泡巨噬細胞 （ Alveolar macrophages；AM ） ……………4
2. 1. 1 肺泡巨噬細胞的來源 ……………………………………...4
2. 1. 2 肺泡巨噬細胞的功能 ………………………………….......4
2. 2 樹狀突細胞 （Dendritic cell；DC） …………………………...5
2. 2. 1 樹狀突細胞的分化來源 …………………………………...6
2. 2. 2 樹狀突細胞之成熟 ………………………………………...7
2. 2. 3 樹狀突細胞功能 …………………………………………...7
2. 3 類鐸接受體 ( Toll-like receptor；TLR ) ………………………..7
2. 3. 1 TLR2的作用 ……………………………………………....8
2. 3. 2 TLR3的作用 ……………………………………………....9
2. 3. 3 TLR4的作用 ……………………………………………....9
2. 3. 4 TLR7與TLR8的作用 …………………………………….10
2. 3. 5 TLR9的作用 ………………………………………….…...10
2. 3. 6 TLR之訊息傳遞路徑 ………………………………….….11
2. 4 豬生殖與呼吸綜合症病毒 ( porcine reproductive and respiratory syndrome virus；PRRSV ) …………………………..12
2. 4. 1 PRRSV結構 ………………………………………….……12
2. 4. 2 PRRSV 感染豬之後的臨床症狀 …………………….…...13
2. 4. 3 PRRSV 感染的臨床病理學、傳播途徑與分離 ………….13
2. 5 細胞激素 ( cytokine ) ..…………………………………….…....14
2. 5. 1 促發炎性細胞激素 ( Pro-inflammatory cytokines ) ….…...14
2. 5. 1. 1 Interleukin-1 ( IL-1 ) ………...……………………..….14
2. 5. 1. 2 Interleukin-6 ( IL-6 ) ………………………………….15
2. 5. 1. 3 腫瘤壞死因子 ( Tumor necrosis factor；TNF ) …..…16
2. 5. 2 趨化激素與干擾素α ( chemokines and interferon-α ) ….…17
2. 5. 2. 1 Interleukin-8 ( IL-8 ) ……………………………….….17
2. 5. 2. 2 單核球趨化蛋白 ( monocyte chemoattractant
protein-1 ) ……………….……………………………..18
2. 5. 2. 3 干擾素α ( Interferon-α；IFN-α ) ..…...………………...19
2. 5. 3 Th1細胞激素 ( Th1 cytokines ) ……………………….…..20
2. 5. 3. 1 Interleukin-12 ( IL-12 ) …..……………………………20
2. 5. 3. 2 Interferon-γ ( IFN-γ ) …..……………………………...20
2. 5. 4 Th2細胞激素 ( Th2 cytokines ) ……………………….…..21
2. 5. 4. 1 Interleukin-4 ( IL-4 ) …………………………………..21
2. 5. 4. 2 Interleukin-10 ( IL-10 ) …..……………………………21
第 3 章 研究之方法與步驟 ……………………………………………23
3. 1 實驗流程 ………………………………………………………..23
3. 2 實驗豬隻 ………………………………………………………..24
3. 3 豬隻骨髓造血幹細胞衍生之未成熟樹狀突細胞之分離
、純化及培養 …..………………………………………………...24
3. 4 分離、培養與純化肺泡巨噬細胞 ………………………………25
3. 5 豬生殖與呼吸綜合症病毒 ( PRRSV ) 的來源與病毒力
價測定 ….………………………………………………………..25
3. 6 以PRRSV感染BMHC-imDC和肺泡巨噬細胞 ………………25
3. 7 細胞RNA的萃取 ……………………………………………….26
3. 8 反轉錄反應 ( reverse transcription ) ……………………….…...26
3. 9 豬隻TLRs及細胞激素mRNA標準陽性樣品 ………………...27
3. 10 以反轉錄聚合酶鏈反應 ( RT-PCR ) 定量TLRs和細胞
激素mRNA ….…………………………………………………...27
3. 11 即時定量聚合酶鏈反應 ( Real-time PCR ) 檢測TLR與
細胞激素 ….……………………………………………………..30
3. 12 統計方法 ………………………….……………………………..32

第 4 章 結 果 …………………………………………………….…33
4. 1 以RT-PCR定量豬隻TLRs及細胞激素mRNA之條件
設定 ……………………………………………………………...33
4. 2 以RT-PCR檢測PRRSV感染樹狀突細胞與巨噬細胞
後其TLRs的mRNA表現量 ….………………………………...34
4. 3 以RT-PCR檢測PRRSV感染樹狀突細胞與巨噬細胞
後其促發炎 細胞激素 ( pro-inflammatory cytokines )、
趨化激素 ( chemokines ) 及IFN-α的mRNA表現量 …...……38
4. 4 以RT-PCR檢測PRRSV感染樹狀突細胞與巨噬細胞
後其 Th1細胞激素的mRNA表現量 …...……………………..41
4. 5 以RT-PCR檢測PRRSV感染樹狀突細胞與巨噬細胞
後其Th2細胞激素的mRNA表現量 ……………………..…….44
4. 6 以Real-time PCR定量TLR3、IL-10與IL-12p40之
mRNA表現量 …………………………………………………..47
4. 7 以Real-time PCR及RT-PCR定量TLR3、IL-10 及
IL-12p40之mRNA結果之相關性分析 …….………………….51
第 5 章 討 論 ………………………………………………….……52
参考文獻 ………………...…………………………………………………56
附 錄 ……………………………………………………………….…..71
作者簡介 ……………………………………………………………….…..73

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