巨噬细胞接触依赖性杀伤机制的研究及活化相关膜蛋白的鉴定

发布时间：2018-02-12 06:55

本文关键词： 巨噬细胞接触依赖性杀伤机制巨噬细胞活化蛋白质组质谱　出处：《吉林大学》2007年博士论文　论文类型：学位论文

【摘要】： 本研究用多聚甲醛固定的卡介苗活化巨噬细胞作为效应细胞,对巨噬细胞接触依赖性肿瘤细胞杀伤机制进行研究,证明了卡介苗活化巨噬细胞存在TNF-α之外的接触依赖性杀伤途径。在此基础上,对活化巨噬细胞膜蛋白进行了大规模鉴定,鉴定出iNOS、TNF-α、F4/80、CD11b、CD14、CD18、CD86、CD44、CD16等大多数已知巨噬细胞活化标志蛋白及表面抗原,证明了研究方法的可行性;同时鉴定出相当数量的新蛋白,更体现了本研究的特色和鉴定结果的潜在价值。在鉴定出的454种活化巨噬细胞特异表达的蛋白分子中,包括117种GOA注释的膜蛋白分子。其中包括高表达的iNOS,这一发现为NO在接触依赖性杀伤过程中的作用机制提供了合理解释。本研究鉴定出的大量活化相关蛋白分子,为深入研究巨噬细胞活化及接触依赖性杀伤机制提供了宝贵资料。作为下一阶段对目标蛋白进行功能研究的开始,我们选取了一个全新蛋白(将其命名为NMAAP1),克隆了该蛋白的基因并构建了原核表达载体,为进一步研究功能奠定了基础。本研究为巨噬细胞接触依赖性杀伤机制的研究及新型表面抗原的鉴定提供了新思路,按照这种思路研究下去,将进一步揭示巨噬细胞活化及接触依赖性杀伤机制,而且极有可能发现新型杀伤效应分子及新型表面抗原,催生新型抗肿瘤药物。
[Abstract]:In this study, macrophages were activated by BCG vaccine fixed with paraformaldehyde as effector cells, and the killing mechanism of macrophages exposed to tumor cells was studied. It was proved that BCG activated macrophages had a contact dependent killing pathway other than TNF- 伪. On this basis, the activated macrophage membrane proteins were identified on a large scale, and the majority of known macrophage activation marker proteins and surface antigens, such as iNOSTNF- 伪 F4 / 80 / CD11bt4 / CD14, CD18, CD86, CD46, CD4, CD16 and so on, were identified, which proved the feasibility of the research method. At the same time, a considerable number of new proteins were identified, which reflected the characteristics of this study and the potential value of the identification results. Among the 454 protein molecules specifically expressed by activated macrophages, This discovery provides a reasonable explanation for the role of no in the process of exposure dependent killing. A large number of activated protein molecules identified in this study have been identified. It provides valuable information for the further study of the mechanism of macrophage activation and contact dependent killing. It is the beginning of the functional study of the target protein in the next stage. We selected a novel protein (named NMAAP1), cloned its gene and constructed prokaryotic expression vector, which laid a foundation for further study of its function. This study provides a new idea for the study of the mechanism of contact dependent killing of macrophages and the identification of new surface antigens. According to this way of thinking, the mechanism of macrophage activation and contact dependent killing will be further revealed. And it is very possible to find new killer molecules and new surface antigens to produce new anti-tumor drugs.
【学位授予单位】：吉林大学
【学位级别】：博士
【学位授予年份】：2007
【分类号】：R392

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