本文關鍵詞： 巨噬細胞 接觸依賴性殺傷機制 巨噬細胞活化蛋白質組 質譜　出處：《吉林大學》2007年博士論文　論文類型：學位論文

【摘要】： 本研究用多聚甲醛固定的卡介苗活化巨噬細胞作為效應細胞,對巨噬細胞接觸依賴性腫瘤細胞殺傷機制進行研究,證明了卡介苗活化巨噬細胞存在TNF-α之外的接觸依賴性殺傷途徑。 在此基礎上,對活化巨噬細胞膜蛋白進行了大規(guī)模鑒定,鑒定出iNOS、TNF-α、F4/80、CD11b、CD14、CD18、CD86、CD44、CD16等大多數(shù)已知巨噬細胞活化標志蛋白及表面抗原,證明了研究方法的可行性;同時鑒定出相當數(shù)量的新蛋白,更體現(xiàn)了本研究的特色和鑒定結果的潛在價值。在鑒定出的454種活化巨噬細胞特異表達的蛋白分子中,包括117種GOA注釋的膜蛋白分子。其中包括高表達的iNOS,這一發(fā)現(xiàn)為NO在接觸依賴性殺傷過程中的作用機制提供了合理解釋。本研究鑒定出的大量活化相關蛋白分子,為深入研究巨噬細胞活化及接觸依賴性殺傷機制提供了寶貴資料。作為下一階段對目標蛋白進行功能研究的開始,我們選取了一個全新蛋白(將其命名為NMAAP1),克隆了該蛋白的基因并構建了原核表達載體,為進一步研究功能奠定了基礎。 本研究為巨噬細胞接觸依賴性殺傷機制的研究及新型表面抗原的鑒定提供了新思路,按照這種思路研究下去,將進一步揭示巨噬細胞活化及接觸依賴性殺傷機制,而且極有可能發(fā)現(xiàn)新型殺傷效應分子及新型表面抗原,催生新型抗腫瘤藥物。
[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- 偽. 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- 偽 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.
【學位授予單位】：吉林大學
【學位級別】：博士
【學位授予年份】：2007
【分類號】：R392

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1 張領兵;巨噬細胞接觸依賴性殺傷機制的研究及活化相關膜蛋白的鑒定[D];吉林大學;2007年

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本文編號：1505040