本文選題：巨噬細(xì)胞　切入點(diǎn)：Rab6　出處：《浙江大學(xué)》2016年博士論文　論文類型：學(xué)位論文

【摘要】：巨噬細(xì)胞是參與體內(nèi)組織防御和穩(wěn)態(tài)維持的一群重要的免疫細(xì)胞,一方面它可以利用吞噬作用來(lái)殺死和清除病原體、細(xì)胞碎片及損傷組織,另一方面它可以激發(fā)獲得性免疫反應(yīng)從而發(fā)揮進(jìn)一步的功能。巨噬細(xì)胞具有異質(zhì)性,在不同環(huán)境信號(hào)刺激下呈現(xiàn)不同表型和功能。目前根據(jù)參與的免疫應(yīng)答反應(yīng)將巨噬細(xì)胞分為經(jīng)典活化的巨噬細(xì)胞(M1型)和替代性活化的巨噬細(xì)胞(M2型)。M1型巨噬細(xì)胞主要參與1型輔助T細(xì)胞(Th1)抗病原的免疫應(yīng)答反應(yīng),可有效殺死病原菌和腫瘤細(xì)胞；而M2巨噬細(xì)胞抑制免疫反應(yīng)和獲得性免疫應(yīng)答,參與血管生成、組織重排和修復(fù)等過(guò)程。腫瘤組織中的巨噬細(xì)胞[腫瘤相關(guān)巨噬細(xì)胞(tumor associated macrophages, TAM)]多呈現(xiàn)M2表型,它們并非發(fā)揮抗腫瘤作用,而是可以促進(jìn)腫瘤發(fā)生、增值、入侵和轉(zhuǎn)移等過(guò)程,并且與腫瘤組織中血管生成有密切關(guān)系。因此,研究M1型巨噬細(xì)胞在免疫中的作用以及M2巨噬細(xì)胞在腫瘤發(fā)展中的作用對(duì)理解異質(zhì)的巨噬細(xì)胞的不同功能具有積極的意義。M1型巨噬細(xì)胞作為專業(yè)的吞噬細(xì)胞,在抗菌感染過(guò)程中發(fā)揮著重要的作用。在組織被病原感染之后,最先響應(yīng)的巨噬細(xì)胞通常呈現(xiàn)出炎性表型并分泌大量的促炎分子。巨噬細(xì)胞的吞噬作用是動(dòng)物進(jìn)化中較保守的細(xì)胞生理活動(dòng),主要行使防御病原菌侵染宿主和起始獲得性免疫應(yīng)答的功能。Rab蛋白是細(xì)胞質(zhì)中囊泡運(yùn)輸?shù)姆肿娱_(kāi)關(guān),目前發(fā)現(xiàn)多種Rab蛋白參與吞噬過(guò)程。本實(shí)驗(yàn)室前期研究表明,在無(wú)脊椎動(dòng)物對(duì)蝦和果蠅中,Rab6蛋白通過(guò)直接與肌動(dòng)蛋白互作來(lái)調(diào)控細(xì)胞吞噬作用,從而抵抗病毒的感染。但是,Rab6蛋白在哺乳動(dòng)物吞噬作用中的功能尚不清楚。本論文以小鼠巨噬細(xì)胞RAW 264.7為研究對(duì)象,探索了小G蛋白R(shí)ab6在哺乳動(dòng)物吞噬過(guò)程中的作用。研究結(jié)果顯示,Rab6蛋白不直接影響巨噬細(xì)胞對(duì)金黃色葡萄球菌的攝取,而是參與胞內(nèi)吞噬小體的成熟過(guò)程。Rab6蛋白與其效應(yīng)蛋白BICD1相互作用,調(diào)控巨噬細(xì)胞內(nèi)吞噬小體成熟的中后期,這一作用機(jī)制與無(wú)脊椎動(dòng)物不同。Rab6蛋白參與的吞噬作用對(duì)吞入的金黃色葡萄球菌在胞內(nèi)的存活也有消極的影響。通過(guò)非活性和活性狀態(tài)的轉(zhuǎn)變以及與驅(qū)動(dòng)蛋白復(fù)合物的相互作用,Rab6蛋白可以在時(shí)空上控制馬達(dá)蛋白介導(dǎo)的運(yùn)輸過(guò)程和細(xì)胞內(nèi)結(jié)構(gòu)的融合過(guò)程。因此,本論文揭示了小G蛋白R(shí)ab6在調(diào)控哺乳動(dòng)物巨噬細(xì)胞抗菌免疫中的重要作用。另一方面,我們研究了M2型巨噬細(xì)胞在腫瘤轉(zhuǎn)移中的作用。在腫瘤組織中,除了腫瘤細(xì)胞之外還存在其他類型的細(xì)胞,包括成纖維細(xì)胞、內(nèi)皮細(xì)胞和免疫細(xì)胞,這些細(xì)胞共同組成腫瘤微環(huán)境。腫瘤組織中最重要的免疫細(xì)胞是巨噬細(xì)胞,且多呈現(xiàn)M2表型。本論文中免疫組織化學(xué)染色結(jié)果顯示,胃癌組織周圍聚集大量的M2型巨噬細(xì)胞,說(shuō)明腫瘤細(xì)胞將巨噬細(xì)胞招募至組織中,并誘導(dǎo)其分化為M2表型。TAM通過(guò)分泌細(xì)胞因子參與腫瘤發(fā)展的調(diào)控,但是目前關(guān)于巨噬細(xì)胞分泌蛋白在腫瘤發(fā)生中的作用研究仍然較少。本文的細(xì)胞試驗(yàn)和動(dòng)物試驗(yàn)結(jié)果顯示,M2型巨噬細(xì)胞大量分泌的幾丁質(zhì)酶3樣蛋白1 (CHI3L1)具有促腫瘤轉(zhuǎn)移的活性。通過(guò)GST下拉試驗(yàn),我們尋找到與CHI3L1結(jié)合的腫瘤細(xì)胞膜上的受體——白介素13受體a2 (IL-13Rα2);細(xì)胞免疫熒光和免疫共沉淀試驗(yàn)證明了兩者之間的直接互作。由此可知,CHI3L1蛋白通過(guò)與腫瘤細(xì)胞膜上的IL-13Rα2受體相互作用,進(jìn)而促進(jìn)腫瘤細(xì)胞的遷移、粘附和入侵,以達(dá)到促腫瘤轉(zhuǎn)移的目的。研究結(jié)果顯示,CHI3L1蛋白處理腫瘤細(xì)胞后,IL-13Rα2受體的激活觸發(fā)細(xì)胞內(nèi)絲裂原活化蛋白激酶(MAPK)信號(hào)通路,引起細(xì)胞外調(diào)節(jié)蛋白激酶1和2(ERK1/2)和c-Jun氨基末端激酶(JNK)蛋白磷酸化水平的升高,進(jìn)而促進(jìn)激活蛋白1(AP-1)家族轉(zhuǎn)錄因子在細(xì)胞核內(nèi)的聚集。AP-1家族轉(zhuǎn)錄因子可以結(jié)合在基質(zhì)金屬蛋白酶(MMP)基因的啟動(dòng)子區(qū)域,從而促進(jìn)MMP家族基因的轉(zhuǎn)錄。腫瘤細(xì)胞分泌的MMP可以有效降解基底膜和周圍的胞外基質(zhì),使纖連蛋白暴露于腫瘤細(xì)胞之間,從而促進(jìn)腫瘤細(xì)胞的粘附和轉(zhuǎn)移。與此同時(shí),動(dòng)物試驗(yàn)結(jié)果表明CHI3L1蛋白具有促腫瘤轉(zhuǎn)移的功能。因此,巨噬細(xì)胞中的CHI3L1蛋白可以作為腫瘤治療的新靶點(diǎn)。我們采用免疫共沉淀與Western blot相結(jié)合的方法來(lái)檢測(cè)入血清樣品中CHI3L1蛋白的含量,結(jié)果顯示,乳腺癌和胃癌病人血清中CHI3L1蛋白的含量較高,而正常人血清中CHI3L1蛋白檢測(cè)不到。此前有研究報(bào)道,在乳腺癌和肺癌中,癌癥病人血清中HER2和C反應(yīng)蛋白的含量明顯高于健康人,并可作為腫瘤診斷的標(biāo)志物。由此可見(jiàn),血清中的CHI3L1蛋白有望成為診斷乳腺癌和胃癌的標(biāo)志蛋白。在了解了M2型巨噬細(xì)胞分泌的CHI3L1蛋白促腫瘤轉(zhuǎn)移的作用機(jī)制后,我們以CHI3L1基因作為靶點(diǎn),探索對(duì)蝦microRNA (miRNA)在跨物種調(diào)控人類腫瘤轉(zhuǎn)移中的作用。為了研究對(duì)蝦miRNA能否跨物種調(diào)控人腫瘤的轉(zhuǎn)移,我們?cè)贛2型巨噬細(xì)胞內(nèi)過(guò)表達(dá)對(duì)蝦miRNA,進(jìn)而檢測(cè)腫瘤細(xì)胞轉(zhuǎn)移能力的變化。我們利用生物信息學(xué)軟件預(yù)測(cè)了三條可能與人CHI3L1 mRNA 3'UTR(3'非編碼區(qū))相互作用的對(duì)蝦特有的miRNA——mja-miR-35、mja-miR-36、mja-miR-37。細(xì)胞轉(zhuǎn)染以及靶基因驗(yàn)證試驗(yàn)表明,對(duì)蝦mja-miR-35可以直接作用于CHI3L1 mRNA 3'UTR,敲低巨噬細(xì)胞內(nèi)CHI3L1基因的表達(dá),并減少分泌到胞外的CHI3L1蛋白的含量,從而影響巨噬細(xì)胞對(duì)腫瘤細(xì)胞轉(zhuǎn)移的促進(jìn)作用。但是mja-miR-36和mja-miR-37并不能有效敲低CHI3L1基因的表達(dá)量。凝膠遷移阻滯試驗(yàn)顯示,人AG02蛋白與這三條miRNA均能結(jié)合,說(shuō)明AG02蛋白與miRNA的結(jié)合沒(méi)有序列和物種選擇性。我們推測(cè)mja-miR-36、mja-miR-37與AG02蛋白的結(jié)合可能改變了AG02蛋白的構(gòu)象,從而抑制了AG02蛋白介導(dǎo)的靶基因降解過(guò)程。對(duì)蝦作為重要的水產(chǎn)品之一,由于感染對(duì)蝦白斑綜合癥病毒(WSSV)引起的對(duì)蝦大量死亡是對(duì)蝦養(yǎng)殖的難題。近幾年研究發(fā)現(xiàn),siRNA和miRNA參與對(duì)蝦的抗病毒免疫。我們通過(guò)研究發(fā)現(xiàn),對(duì)蝦mja-miR-35可以作用于WSSV病毒基因,從而抑制病毒在對(duì)蝦體內(nèi)的復(fù)制及感染,促進(jìn)對(duì)蝦的抗病毒免疫。這些結(jié)果說(shuō)明,對(duì)蝦mja-miR-35既能調(diào)控對(duì)蝦抗病毒免疫,又能跨物種調(diào)控人類腫瘤細(xì)胞的轉(zhuǎn)移。本論文圍繞巨噬細(xì)胞在抗菌免疫以及促進(jìn)腫瘤轉(zhuǎn)移中的功能展開(kāi)研究。首先通過(guò)研究小G蛋白R(shí)ab6在哺乳動(dòng)物M1型巨噬細(xì)胞吞噬過(guò)程中的作用,我們發(fā)現(xiàn)Rab6蛋白能調(diào)控吞噬小體的成熟過(guò)程。其次,我們闡明了腫瘤細(xì)胞可以招募M2型巨噬細(xì)胞以及M2型巨噬細(xì)胞大量分泌的CHI3L1蛋白進(jìn)一步促進(jìn)腫瘤轉(zhuǎn)移的作用機(jī)制。因此,本文的研究結(jié)果對(duì)理解巨噬細(xì)胞在抗菌免疫以及腫瘤轉(zhuǎn)移中的功能具有重要意義。最后,我們發(fā)現(xiàn)一條對(duì)蝦miRNA——mja-miR-35,該miRNA既能調(diào)控對(duì)蝦抗病毒免疫,又能跨物種調(diào)控人類腫瘤細(xì)胞的轉(zhuǎn)移。
[Abstract]:Macrophages are the immune cells involved in tissue defense and homeostasis maintained a group of important, on the one hand it can be used to kill and eliminate pathogens phagocytosis, cell debris and tissue damage, on the other hand, it can stimulate the acquired immune response and play a further function. Macrophages are heterogeneous and exhibit different phenotype and function in different environment according to the current signal stimulation. The immune response in macrophages into classically activated macrophages (M1) and alternatively activated macrophages (M2).M1 macrophages mainly involved in type 1 T helper cell (Th1) antiviral immune response the reaction, which can effectively kill pathogens and tumor cells; M2 inhibition of macrophage immune response and acquired immune response, angiogenesis, tissue repair and rearrangement process. In tumor tissue macrophages [tumor Related (tumor associated macrophages, macrophage TAM)] showed M2 phenotype, they do not exert anti-tumor effect, but added can promote tumorigenesis, invasion and metastasis process, and vascular tumor formation are closely related. Therefore, different functions of macrophages induced inhibition of M1 macrophages in immunity and M2 macrophages in tumor development in understanding the heterogeneity of the significance of.M1 positive macrophages as professional phagocytes, antibacterial infection plays an important role in the process. After the organization was the first response to pathogen infection, macrophages are usually inflammatory phenotype and secretion of proinflammatory molecules. The phagocytosis of macrophage is a relatively conserved cellular physiological activity in animal evolution, the main pathogen infection and host defense exercise initiation acquired immune response. .Rab protein is vesicular transport in the cytoplasm of the molecular switch, found that many Rab proteins involved in the phagocytic process. Our previous study showed that in invertebrates, shrimp and Drosophila, Rab6 protein through direct interaction with actin to regulate cell phagocytosis, and resistance to virus infection. However, the function of Rab6 protein in mammalian phagocytosis in is not clear. The mouse macrophage RAW 264.7 as the research object, to explore the small G protein Rab6 in mammalian phagocytic process. The results showed that the Rab6 protein does not directly affect the uptake of macrophages on Staphylococcus aureus, but interactions involved in intracellular phagosome maturation process of.Rab6 protein and its effect BICD1 protein, regulation of macrophage phagosome maturation in the late, this mechanism with different.Rab6 proteins in invertebrates The phagocytosis of ingestion of Staphylococcus aureus in intracellular survival can also have a negative impact. Through the transformation of non active and active state and interaction with kinesin complexes, Rab6 protein can control the transport process of motor proteins and cell fusion mediated within the structure of the process in time and space. Therefore, the this paper reveals the small G protein Rab6 in regulating mammalian macrophages play an important role in antibacterial immunity. On the other hand, we study the M2 type macrophage function in tumor metastasis. In tumor tissues, in addition to the tumor cells also exist in other cell types, including fibroblasts, endothelial cells and immune cells, these the cell is composed of the tumor microenvironment in tumor tissue. The most important immune cells are macrophages, and showed M2 phenotype. The immunohistochemical staining results showed that the gastric cancer group A large number of fabric gathered around M2 macrophages, tumor cells will explain macrophage recruitment to the tissue, and induce the differentiation phenotype of M2.TAM regulates secretion of cytokines involved in tumor development through, but the current research on the role of macrophage secretory protein in tumorigenesis is still small. The cell and animal experiments results in this paper show that M2 a large number of macrophages secrete 3 chitinase like protein 1 (CHI3L1) can promote tumor metastasis activity. Through the GST drop-down test, we find the tumor cell membrane and CHI3L1 binding on the receptor - interleukin 13 receptor A2 (IL-13R alpha 2); test between direct immunofluorescence and immune interaction co precipitation. Therefore, CHI3L1 protein with tumor cell membrane IL-13R alpha 2 receptor interaction, thereby promoting tumor cell migration, adhesion and invasion, in order to To promote tumor metastasis. The results of the study showed that CHI3L1 protein in tumor cells after activation of IL-13R alpha 2 receptors trigger intracellular mitogen activated protein kinase (MAPK) signaling pathway induced by extracellular regulated protein kinase 1 and 2 (ERK1/2) and c-Jun N-terminal kinase (JNK) phosphorylation level increased. And then promote the activator protein 1 (AP-1) family of transcription factors in the nucleus of the aggregation of.AP-1 family transcription factors bind to matrix metalloproteinase (MMP) gene promoter, so as to promote the transcription of MMP gene family. The extracellular matrix secreted by tumor cells, MMP can effectively degrade the basement membrane and the surrounding, the fibronectin exposure to tumor cells, so as to promote the adhesion and metastasis of tumor cells. At the same time, animal experiment results show that CHI3L1 protein can promote tumor metastasis. Therefore, macrophage CHI3L1 in eggs A new target white can be used as tumor therapy. We use the content of CO immunoprecipitation method combined with Western blot to detect CHI3L1 protein in serum samples showed higher content of serum CHI3L1 protein in patients with breast cancer and gastric cancer, and the detection of CHI3L1 protein in normal human serum. Previous studies have reported that in breast cancer and lung cancer, cancer, HER2 and C content in serum of patients with C-reactive protein was significantly higher than that of healthy people, and can be used as a marker of tumor diagnosis. Thus, the serum CHI3L1 protein is expected to become a diagnosis of breast cancer and gastric cancer marker protein. In the understanding of the M2 type macrophage CHI3L1 protein promoting mechanism tumor metastasis, we used CHI3L1 as a target gene, microRNA (miRNA) to explore the shrimp in cross species regulation of human tumor metastasis. In order to study whether miRNA can cross species of shrimp Regulation of human tumor metastasis, we overexpressed miRNA in shrimp M2 macrophages, and detecting the changes of metastatic ability of tumor cells. We use bioinformatics software predicted three possible CHI3L1 mRNA 3'UTR (3'and non encoding regions) the interaction of shrimp specific miRNA - mja-miR-35, mja-miR-36, showed that mja-miR-37. cell transfection and the target gene test, shrimp mja-miR-35 can have a direct effect on the CHI3L1 mRNA 3'UTR on CHI3L1 gene expression in macrophages is low, and reduce the content of extracellular CHI3L1 protein, thus affecting macrophages on tumor cell metastasis promoting effect. But mja-miR-36 and mja-miR-37 can not effectively at low expression of CHI3L1 gene of the gel. Transfer block test showed that the human AG02 protein and the three miRNA can be combined with AG02 and miRNA protein showed no sequence and species selection Optional. We speculate that mja-miR-36, the combination of mja-miR-37 and AG02 protein may alter the conformation of AG02 protein, thus inhibiting the degradation of target genes mediated by AG02 protein. The shrimp is one of the important aquatic products, due to the infection of white spot syndrome virus (WSSV) caused by the death of a large number of shrimp shrimp farming is a difficult problem in recent. Years of research found that siRNA and miRNA are involved in antiviral immunity of shrimp. We found that the shrimp mja-miR-35 can act on the WSSV virus gene, thereby inhibiting virus replication and infection in shrimp body, promote the antiviral immunity of shrimp. These results suggest that the shrimp mja-miR-35 can both regulate the antiviral immunity of shrimp, and cross species transfer regulation of human tumor cells. This paper focuses on the research on macrophage antibacterial immunity and promote tumor metastasis function. First through the study of small G protein Rab 6 macrophages in mammalian type M1 in the process of phagocytosis, we found that Rab6 protein can regulate phagosome maturation process. Secondly, we clarify the tumor cells can recruit M2 macrophages and M2 macrophages to secrete CHI3L1 protein to further promote the mechanism of tumor metastasis. Therefore, the results of this study have important understanding of macrophage in the antibacterial immunity and function in tumor metastasis. Finally, we found a miRNA - mja-miR-35, the miRNA can control the antiviral immunity of shrimp, and cross species transfer regulation of human tumor cells.

【學(xué)位授予單位】：浙江大學(xué)
【學(xué)位級(jí)別】：博士
【學(xué)位授予年份】：2016
【分類號(hào)】：R73-37

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1 ;豚鼠巨噬細(xì)胞經(jīng)P_(204)處理后的抗石英細(xì)胞毒作用[J];國(guó)外醫(yī)學(xué)參考資料(衛(wèi)生學(xué)分冊(cè));1976年04期

2 鄧俠進(jìn);;巨噬細(xì)胞的抗癌作用[J];遵義醫(yī)學(xué)院學(xué)報(bào);1979年02期

3 陸天才;;疾病對(duì)肺巨噬細(xì)胞的影響[J];煤礦醫(yī)學(xué);1982年01期

4 郭瑞清;祝彼得;;一種分離巨噬細(xì)胞的簡(jiǎn)單方法[J];濱州醫(yī)學(xué)院學(xué)報(bào);1990年02期

5 謝志堅(jiān);巨噬細(xì)胞異質(zhì)性[J];醫(yī)學(xué)綜述;2001年06期

6 饒艷;運(yùn)動(dòng)及神經(jīng)內(nèi)分泌對(duì)巨噬細(xì)胞功能的調(diào)節(jié)[J];體育與科學(xué);2002年05期

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9 韋錦學(xué);顧軍;;巨噬細(xì)胞的激活誘導(dǎo)死亡[J];生命科學(xué);2006年02期

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