本文選題：趨化因子　切入點(diǎn)：CCL18　出處：《吉林大學(xué)》2006年博士論文　論文類型：學(xué)位論文

【摘要】：本研究通過體外實(shí)驗(yàn)以及應(yīng)用人體化的重癥聯(lián)合免疫缺陷(SCID)小鼠進(jìn)行的體內(nèi)實(shí)驗(yàn)對(duì)CCL18在過敏性疾病發(fā)病機(jī)理中的作用進(jìn)行了研究,取得了以下學(xué)術(shù)進(jìn)展: 1.研究發(fā)現(xiàn)在過敏原的刺激下,過敏性哮喘患者外周血單個(gè)核細(xì)胞(PBMC)在轉(zhuǎn)錄及翻譯水平表達(dá)CCL18基因增高。免疫酶聯(lián)及免疫組化檢測進(jìn)一步發(fā)現(xiàn),未經(jīng)治療的過敏性哮喘患者血清及支氣管肺泡盥洗液中CCL18水平顯著增高。發(fā)現(xiàn)CCL18在體外能夠趨化Th2細(xì)胞和嗜堿性粒細(xì)胞。本研究的結(jié)果進(jìn)一步提出了CCL18參與過敏性疾病發(fā)病的科學(xué)依據(jù)。 2.柴油廢氣顆粒(DEP)能夠通過IL-13在轉(zhuǎn)錄及翻譯水平顯著提高CCL18在非過敏者PBMC中的表達(dá),從而導(dǎo)致Th2細(xì)胞的募集。更進(jìn)一步表明CCL18可能在過敏性疾病產(chǎn)生的最初始時(shí)期發(fā)揮致病作用。 3.通過對(duì)CCL5利用CCR5在SCID小鼠模型中募集炎癥細(xì)胞的實(shí)驗(yàn),證明了該模型應(yīng)用于趨化因子研究中的可行性。利用人體化SCID小鼠模型研究的結(jié)果表明CCL18能夠趨化單核/巨噬細(xì)胞、Th2細(xì)胞、原態(tài)和記憶T細(xì)胞。進(jìn)一步通過體內(nèi)實(shí)驗(yàn)證明了CCL18能通過募集Th2細(xì)胞為主的炎癥細(xì)胞來促進(jìn)過敏性疾病的發(fā)生發(fā)展。 4.構(gòu)建了人CCL18及連有人或小鼠IgG1 Fc片段的CCL18的真核表達(dá)載體。經(jīng)擴(kuò)增表達(dá)及克隆選擇后獲得在無血清條件下高效穩(wěn)定表達(dá)的細(xì)胞克隆。為在真核系統(tǒng)中克隆CCL18受體奠定了基礎(chǔ)�？傊�,本研究首次發(fā)現(xiàn)CCL18參與了過敏性哮喘的發(fā)病,并首次揭示了CCL18在過敏性哮喘中的細(xì)胞來源及在過敏性疾病發(fā)病機(jī)制中的重要作用。表明CCL18可能是治療過敏性疾病的潛在分子靶點(diǎn)。
[Abstract]:In this study, the role of CCL18 in the pathogenesis of allergic diseases was studied through in vitro experiments and in vivo experiments in mice with severe combined immunodeficiency syndrome (CCL18), and the following academic advances were made. 1. It was found that the expression of CCL18 gene in peripheral blood mononuclear cells (PBMC) of allergic asthma patients was increased at the level of transcription and translation. The levels of CCL18 in serum and bronchoalveolar lavatory fluid of untreated allergic asthma patients were significantly increased. It was found that CCL18 can chemotactic Th2 cells and basophil in vitro. The results of this study further suggest that CCL18 is involved in allergy. The scientific basis for the onset of sexual diseases. 2. The expression of CCL18 in non-allergic PBMC was significantly increased by IL-13 at transcription and translation level. This leads to the recruitment of Th2 cells, which further indicates that CCL18 may play a pathogenic role in the initial stage of allergic diseases. 3. The experiment of CCL5 using CCR5 to recruit inflammatory cells in SCID mouse model was carried out. The results showed that CCL18 could chemoattractant mononuclear / macrophage Th2 cells. In vivo, CCL18 can promote the development of allergic diseases by recruiting inflammatory cells dominated by Th2 cells. 4. The eukaryotic expression vector of human CCL18 and CCL18 containing human or mouse IgG1 FC fragment was constructed. After amplified expression and clone selection, a cell clone with high and stable expression in serum-free condition was obtained, which was used to clone CCL18 in eukaryotic system. Body laid the foundation. In a word, This study first found that CCL18 was involved in the pathogenesis of allergic asthma. It is the first time to reveal the cellular origin of CCL18 in allergic asthma and its important role in the pathogenesis of allergic diseases, suggesting that CCL18 may be a potential molecular target for the treatment of allergic diseases.
【學(xué)位授予單位】：吉林大學(xué)
【學(xué)位級(jí)別】：博士
【學(xué)位授予年份】：2006
【分類號(hào)】：R363

【共引文獻(xiàn)】

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