趋化因子CCL18在过敏性疾病发病机理中的作用

发布时间：2018-03-05 10:35

本文选题：趋化因子　切入点：CCL18　出处：《吉林大学》2006年博士论文　论文类型：学位论文

【摘要】：本研究通过体外实验以及应用人体化的重症联合免疫缺陷(SCID)小鼠进行的体内实验对CCL18在过敏性疾病发病机理中的作用进行了研究,取得了以下学术进展: 1.研究发现在过敏原的刺激下,过敏性哮喘患者外周血单个核细胞(PBMC)在转录及翻译水平表达CCL18基因增高。免疫酶联及免疫组化检测进一步发现,未经治疗的过敏性哮喘患者血清及支气管肺泡盥洗液中CCL18水平显著增高。发现CCL18在体外能够趋化Th2细胞和嗜碱性粒细胞。本研究的结果进一步提出了CCL18参与过敏性疾病发病的科学依据。 2.柴油废气颗粒(DEP)能够通过IL-13在转录及翻译水平显著提高CCL18在非过敏者PBMC中的表达,从而导致Th2细胞的募集。更进一步表明CCL18可能在过敏性疾病产生的最初始时期发挥致病作用。 3.通过对CCL5利用CCR5在SCID小鼠模型中募集炎症细胞的实验,证明了该模型应用于趋化因子研究中的可行性。利用人体化SCID小鼠模型研究的结果表明CCL18能够趋化单核/巨噬细胞、Th2细胞、原态和记忆T细胞。进一步通过体内实验证明了CCL18能通过募集Th2细胞为主的炎症细胞来促进过敏性疾病的发生发展。 4.构建了人CCL18及连有人或小鼠IgG1 Fc片段的CCL18的真核表达载体。经扩增表达及克隆选择后获得在无血清条件下高效稳定表达的细胞克隆。为在真核系统中克隆CCL18受体奠定了基础。总之,本研究首次发现CCL18参与了过敏性哮喘的发病,并首次揭示了CCL18在过敏性哮喘中的细胞来源及在过敏性疾病发病机制中的重要作用。表明CCL18可能是治疗过敏性疾病的潜在分子靶点。
[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.
【学位授予单位】：吉林大学
【学位级别】：博士
【学位授予年份】：2006
【分类号】：R363

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