發(fā)布時(shí)間：2018-02-12 06:55

  本文關(guān)鍵詞： 巨噬細(xì)胞 接觸依賴性殺傷機(jī)制 巨噬細(xì)胞活化蛋白質(zhì)組 質(zhì)譜　出處：《吉林大學(xué)》2007年博士論文　論文類型：學(xué)位論文

【摘要】： 本研究用多聚甲醛固定的卡介苗活化巨噬細(xì)胞作為效應(yīng)細(xì)胞,對(duì)巨噬細(xì)胞接觸依賴性腫瘤細(xì)胞殺傷機(jī)制進(jìn)行研究,證明了卡介苗活化巨噬細(xì)胞存在TNF-α之外的接觸依賴性殺傷途徑。 在此基礎(chǔ)上,對(duì)活化巨噬細(xì)胞膜蛋白進(jìn)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(xì)胞活化標(biāo)志蛋白及表面抗原,證明了研究方法的可行性;同時(shí)鑒定出相當(dāng)數(shù)量的新蛋白,更體現(xiàn)了本研究的特色和鑒定結(jié)果的潛在價(jià)值。在鑒定出的454種活化巨噬細(xì)胞特異表達(dá)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(dá)的iNOS,這一發(fā)現(xiàn)為NO在接觸依賴性殺傷過(guò)程中的作用機(jī)制提供了合理解釋。本研究鑒定出的大量活化相關(guān)蛋白分子,為深入研究巨噬細(xì)胞活化及接觸依賴性殺傷機(jī)制提供了寶貴資料。作為下一階段對(duì)目標(biāo)蛋白進(jìn)行功能研究的開(kāi)始,我們選取了一個(gè)全新蛋白(將其命名為NMAAP1),克隆了該蛋白的基因并構(gòu)建了原核表達(dá)載體,為進(jìn)一步研究功能奠定了基礎(chǔ)。 本研究為巨噬細(xì)胞接觸依賴性殺傷機(jī)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(jìn)一步揭示巨噬細(xì)胞活化及接觸依賴性殺傷機(jī)制,而且極有可能發(fā)現(xiàn)新型殺傷效應(yīng)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(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】：2007
【分類號(hào)】：R392

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1 張領(lǐng)兵;巨噬細(xì)胞接觸依賴性殺傷機(jī)制的研究及活化相關(guān)膜蛋白的鑒定[D];吉林大學(xué);2007年

2 倫艷妮;BCG活化小鼠巨噬細(xì)胞膜蛋白質(zhì)組的生物信息學(xué)分析及相關(guān)分子INATase的初步研究[D];吉林大學(xué);2009年

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本文編號(hào)：1505040