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巨噬细胞极化是根据周围刺激环境做出表型调节的一个过程.一般极化为2个表型,分别为经典激活的M1巨噬细胞和替代激活的M2巨噬细胞.简而言之,M1巨噬细胞的特征是促炎和抗肿瘤;M2巨噬细胞是抗炎和促肿瘤.巨噬细胞极化被认为是人体生理和病理的关键调节器,其发挥作用的有效性依赖于关键因子的协调表达,而这些关键因子的表达在转录后...  相似文献   

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张豪博  张莹 《病毒学报》2023,(6):1757-1767
巨噬细胞具有功能可塑性,使其能够根据微环境线索不同极化为不同表型,主要分为两种类型,即促炎M1型巨噬细胞和抗炎M2型巨噬细胞,它们在单纯疱疹病毒1型(Herpes simplex virus-1, HSV-1)感染的疾病发展中行使不同的功能。当巨噬细胞出现极化失衡时,可以通过多种因素对其失衡状态进行调节,靶向调节巨噬细胞的极化状态对于治疗HSV-1感染具有重要意义。本文对巨噬细胞极化及其在HSV-1感染中的作用研究进展进行总结,以期为HSV-1感染的进一步研究及治疗提供参考依据。  相似文献   

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曹春雨  王清  王艳林 《生命科学》2013,(11):1105-1108
肿瘤相关巨噬细胞是肿瘤组织局部浸润的巨噬细胞,在肿瘤组织微环境中,这些巨噬细胞发生M2型极化,从而发挥免疫抑制效应,促进肿瘤增殖。而M2型极化的肿瘤相关巨噬细胞也能够被再次诱导逆向极化形成具有抗肿瘤效应的M1型肿瘤相关巨噬细胞,激发机体产生特异性抗肿瘤免疫应答。促进肿瘤相关巨噬细胞M1型极化由此成为当前抗肿瘤免疫防治研究的热点。将对有关肿瘤相关巨噬细胞极化的新进展进行综述,为抗肿瘤免疫研究提供新的思路。  相似文献   

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[目的]研究艾拉莫德(T-614)对小鼠巨噬细胞(RAW264.7)M1型极化的影响。[方法]细胞毒性实验观察3个浓度(400 g/L,800 g/L,1 200 g/L)的T-614对RAW264.7的影响,使用LPS/IFN-γ诱导RAW264.7发生M1型分化,同时进行T-614干预。流式细胞术检测RAW264.7表面F4/80+CD86+与MHCⅡ+的比例,ELISA检测细胞中IL-1β、IL-6、TNF-α的含量,RT-PCR检测细胞中IL-1β、IL-6、TNF-α、MCP-1、CD86和iNOS基因的表达,Western Blot检测细胞中MCP-1、CD86和iNOS蛋白表达水平。[结果]3个浓度T-614对未分化的巨噬细胞没有毒性;高浓度T-614降低M1巨噬细胞表面的F4/80+CD86+与MHCⅡ+比例(P<0.05),降低MCP-1、CD86和iNOS的基因表达水平与蛋白表达水平(P<0.05),降低IL-1β、IL-6、TNF-α基因表达与减少IL-1β、IL-6、TNF-α的含量(P<0.05)。[结论]T-614能抑制RAW264.7进行M1型极化,抑制MCP-1、CD86和iNOS的表达,减少IL-1β、IL-6、TNF-α的形成与分泌。  相似文献   

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表型可变性和功能多样性是单个核吞噬细胞的重要特征。近年来巨噬细胞的极化受到关注。一般认为极化巨噬细胞是单核细胞活化后一系列功能状态两个极端。而它的分化受到各种微环境信号的诱导与调节。极化的巨噬细胞能够进一步影响局部免疫反应,与各种因子协同作用调节病原体微生物感染结局和肿瘤免疫,参与免疫调节,组织修复重塑过程。对巨噬细胞亚型诱导因素及功能的研究将有助于了解免疫反应的调节机制。  相似文献   

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本文旨在研究巨噬细胞极化过程对自身铁代谢调节的影响.用20 ng/mLγ干扰素(interferon gamma,1FN-γ)刺激猪肺泡巨噬细胞(3D4/2细胞)24 h,诱导其为M1型巨噬细胞,另外用10 ng/mL白细胞介素4(interleukin-4,IL-4)联合10 ng/mL巨噬细胞集落刺激因子(macr...  相似文献   

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目的 本研究旨在探索并阐明芍药甘草汤(Shakuyakukanzoto,SKT)通过调节巨噬细胞的能量代谢和极化来改善小鼠溃疡性结肠炎(ulcerative colitis,UC)的可能作用机制。方法 通过给予3%葡聚糖硫酸钠盐(dextran sulfate sodium salt,DSS)构建小鼠UC模型并通过灌胃SKT进行治疗。首先,对两个数据集GSE21157和GSE210415进行单细胞测序分析和代谢通路富集。其次,对UC小鼠腹腔巨噬细胞的提取和代谢组学验证。然后,根据标准逆方差加权两样本的单变量孟德尔随机化分析差异代谢物富集的通路和UC风险相关性。接着,分析在GSE128682和GSE102746数据集转录水平差异。最后,使用定量反转录PCR(qRT-PCR)、蛋白质印迹法(Western blot)和流式细胞术验证结果。结果 苏木精-伊红(HE)染色结果显示,SKT可以显著缓解DSS引起的结肠损伤。单细胞测序分析在肠壁中发现了巨噬细胞、NK细胞、T细胞等10多种不同类型的细胞。在疾病组中,通过比较这两组数据发现,有49条主要涉及能量代谢的巨噬细胞代谢途径的活性显著上调。能量代谢组学中,治疗组与模型组,模型组与空白组分别鉴定了10种和18种显著上调和下调的差异表达代谢物,这些差异表达的代谢物主要与糖酵解和氧化磷酸化有关。根据标准逆方差加权两样本的单变量孟德尔随机化分析,预测糖酵解和氧化磷酸化相关基因泛醌NADH脱氢酶Fe-S蛋白1(recombinant NADH dehydrogenase ubiquinone Fe-S protein 1,NDUFS1)(OR:0.56,95% CI:0.48~0.98,P=0.000 068)与UC风险降低相关。通过对两组数据集转录水平差异分析,与正常组相比,UC中NDUFS1的转录水平降低。qRT-PCR、Western blot和流式细胞术验证结果显示,SKT可以促进NDUFS1蛋白的表达,抑制巨噬细胞向M1型极化。此外,敲低/过表达NDUFS1可以影响SKT对巨噬细胞M1型极化的影响。结论 SKT通过调节NDUFS1蛋白水平,抑制巨噬细胞向M1型极化,从而缓解小鼠UC。这些发现不仅揭示了SKT对UC的治疗机制,也为临床应用提供了新的理论基础。  相似文献   

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固有免疫是机体抵御病原微生物入侵的第一道防线。巨噬细胞(macrophages, Mφ)在机体中分布广泛并具有十分活跃的生物学功能,在宿主抗病毒固有免疫应答过程中发挥重要作用。既往研究集中于Mφ的吞噬功能及抗原提呈作用,而近年来研究发现,不同活化模式的Mφ对病毒感染后机体的炎症反应具有双重调控作用,Mφ的极化状态与病毒感染性疾病的发生和转归关系密切。病毒感染急性期,Mφ向M1方向极化,M1型Mφ可促进炎症反应,辅助机体清除病原体,但其过度活化可引起细胞因子风暴,加重组织的免疫病理损伤;随着病毒感染相关疾病的进展,Mφ向M2方向极化,M2型Mφ可通过分泌多种抑炎因子发挥免疫调控作用,参与组织修复,亦与感染慢性化密切相关。不同种类的病毒感染机体后可以诱导Mφ向不同方向极化,但其具体调控机制目前尚不清楚。现就Mφ极化在病毒感染过程中的作用及其调控机制作一概述,为相关疾病的发病机制研究奠定理论基础,并为治疗策略的研发提供新的思路。  相似文献   

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Background

Macrophages are traditionally associated with inflammation and host defence, however a greater understanding of macrophage heterogeneity is revealing their essential roles in non-immune functions such as development, homeostasis and regeneration. In organs including the brain, kidney, mammary gland and pancreas, macrophages reside in large numbers and provide essential regulatory functions that shape organ development and maturation. However, the role of macrophages in lung development and the potential implications of macrophage modulation in the promotion of lung maturation have not yet been ascertained.

Methods

Embryonic day (E)12.5 mouse lungs were cultured as explants and macrophages associated with branching morphogenesis were visualised by wholemount immunofluorescence microscopy. Postnatal lung development and the correlation with macrophage number and phenotype were examined using Colony-stimulating factor-1 receptor-enhanced green fluorescent protein (Csf1r-EGFP) reporter mice. Structural histological examination was complemented with whole-body plethysmography assessment of postnatal lung functional maturation over time.Flow cytometry, real-time (q)PCR and immunofluorescence microscopy were performed to characterise macrophage number, phenotype and localisation in the lung during postnatal development. To assess the impact of developmental macrophage modulation, CSF-1 was administered to neonatal mice at postnatal day (P)1, 2 and 3, and lung macrophage number and phenotype were assessed at P5. EGFP transgene expression and in situ hybridisation was performed to assess CSF-1R location in the developing lung.

Results

Macrophages in embryonic lungs were abundant and densely located within branch points during branching morphogenesis. During postnatal development, structural and functional maturation of the lung was associated with an increase in lung macrophage number. In particular, the period of alveolarisation from P14-21 was associated with increased number of Csf1r-EGFP+ macrophages and upregulated expression of Arginase 1 (Arg1), Mannose receptor 1 (Mrc1) and Chemokine C-C motif ligand 17 (Ccl17), indicative of an M2 or tissue remodelling macrophage phenotype. Administration of CSF-1 to neonatal mice increased trophic macrophages during development and was associated with increased expression of the M2-associated gene Found in inflammatory zone (Fizz)1 and the growth regulator Insulin-like growth factor (Igf)1. The effects of CSF-1 were identified as macrophage-mediated, as the CSF-1R was found to be exclusively expressed on interstitial myeloid cells.

Conclusions

This study identifies the presence of CSF-1R+ M2-polarised macrophages localising to sites of branching morphogenesis and increasing in number during the alveolarisation stage of normal lung development. Improved understanding of the role of macrophages in lung developmental regulation has clinical relevance for addressing neonatal inflammatory perturbation of development and highlights macrophage modulation as a potential intervention to promote lung development.  相似文献   

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目的:巨噬细胞是动脉粥样硬化斑块中最丰富的免疫细胞,巨噬细胞泡沫化加速动脉粥样硬化,本研究探讨巨噬细胞自噬与极化对泡沫化的影响。方法:分离培养小鼠腹腔巨噬细胞,免疫荧光检测巨噬细胞的标记物F4/80。不同浓度雷帕霉素处理巨噬细胞,western blot检测自噬标记物LC3II,经典激活的巨噬细胞(Classically activated macrophages, M1)标记物白细胞介素6(interleukin 6, IL-6)和替代激活的巨噬细胞(Alternatively activated macrophages, M2)标记物转化生长因子β(transform growth factor,TGF-β)的表达。用ox-LDL诱导巨噬细胞泡沫化,油红O染色鉴定泡沫细胞形成及巨噬细胞泡沫化情况。结果:免疫荧光结果显示,小鼠腹腔巨噬细胞F4/80阳性率达87.6%;雷帕霉素处理巨噬细胞24 h,western blot结果显示LC3II表达增加,M1标记物IL-6表达增加,而M2标记物TGF-β表达减少,对其条带进行统计分析结果显示都具有显著性差异(P0.05);油红O染色结果显示雷帕霉素明显减少巨噬细胞泡沫化形成。结论:雷帕霉素能诱导巨噬细胞自噬,促进其向M1型极化,从而抑制巨噬细胞泡沫化。  相似文献   

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Macrophages are key cells in the innate immune system. They phagocytose pathogens and cellular debris, promote inflammation, and have important roles in tumor immunity. Depending on the microenvironment, macrophages can polarize to M1 (inflammatory) or M2 (anti-inflammatory) phenotypes. Extracellular DnaK (the bacterial ortholog of the mammalian Hsp70) from Mycobacterium tuberculosis (Mtb) was described to exert immune modulatory roles in an IL-10 dependent manner. We have previously observed that endotoxin-free DnaK can polarize macrophages to an M2-like phenotype. However, the mechanisms that underlie this polarization need to be further investigated. IL-10 has been described to promote macrophage polarization, so we investigated the involvement of this cytokine in macrophages stimulated with extracellular DnaK. IL-10 was required to induce the expression of M2 markers - Ym1 and Fizz, when macrophages were treated with DnaK. Blockade of IL-10R also impaired DnaK induced polarization, demonstrating the requirement of the IL-10/IL-10R signaling pathway in this polarization. DnaK was able to induce TGF-β mRNA in treated macrophages in an IL-10 dependent manner. However, protein TGF-β could not be detected in culture supernatants. Finally, using an in vivo allogeneic melanoma model, we observed that DnaK-treated macrophages can promote tumor growth in an IL-10-dependent manner. Our results indicate that the IL-10/IL-10R axis is required for DnaK-induced M2-like polarization in murine macrophages.  相似文献   

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To investigate whether carrimycin (CAM) affects the occurrence and development of melanoma by regulating the polarization of macrophages, and the following related cell biology assays were used to examine its function. Methods: The effect of CAM on macrophage polarization was detected by real-time quantitative polymerase chain reaction (Q-RT-PCR) and Western blot. Flow cytometry and Cell Counting Kit-8 were used to detect the effect of CAM on mouse macrophages in vitro and in vivo phagocytosis and proliferation. Cell line-derived xenograft model was constructed via B16-F10 to evaluate the anti-tumor effect of CAM on melanoma. Results: In the mRNA level, CAM could up-regulate the levels of TNF-α and iNOS in M1 and down-regulate the level of Arg-1 in M2. In the protein level, CAM can increase the expression of p-STAT1 and decrease the expression of p-STAT3. In the cell line-derived xenograft model, these data shown that the occurrence and CAM development of melanoma was inhibited after CAM treatment, the tumor inhibition rate was 41.6%, and promoted the increase of the number of M1 macrophages (P<0.05). Conclusion: CAM promotes the increase in the number of M1 macrophages in vivo and inhibits the progression of melanoma, suggesting that CAM may achieve anti-tumor effects by inducing the polarization of macrophages to M1.  相似文献   

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目的探讨双歧杆菌对巨噬细胞。ERK1/2蛋白激酶通道的调控。方法收集SD大鼠腹腔巨噬细胞,提取细胞浆蛋白及核蛋白,采用Western印迹分析双歧杆菌对巨噬细胞ERK蛋白激酶水平的影响。结果双歧杆菌呈浓度依赖性诱导巨噬细胞ERK1/2的活化。10^3/ml的双歧杆菌即可增加ERK1/2磷酸化。用10^3/ml的双歧杆菌刺激巨噬细胞,ERK1/2磷酸化30min达到高峰。特异性ERK蛋白激酶抑制剂PD98059能显著降低双歧杆菌诱导的巨噬细胞ERK1/2的活化。结论双歧杆菌可以通过ERK蛋白激酶通道调控巨噬细胞。  相似文献   

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目的:探讨普适泰联合地奥司明治疗老年慢性前列腺炎(CP)的临床效果及对患者血清和前列腺液巨噬细胞炎性蛋白-2(MIP-2)、巨噬细胞炎性蛋白-1α(MIP-1α)水平的影响。方法:选择我院2015年1月~2016年9月收治的126例老年CP患者,采取随机数字表将其分成两组。观察组(63例)给予普适泰联合地奥司明治疗,对照组(63例)予以普适泰治疗。记录比较两组临床疗效,治疗前后血清与前列腺液的MIP-2、MIP-1α水平;评价两组用药安全性。结果:治疗12周后,观察组总有效率为93.7%,较对照组明显升高(81.0%,P0.05)。与治疗前对比,两组治疗12周后血清和前列腺液中MIP-2、MIP-1α水平均显著下降(P0.01);且观察组治疗12周后血清与前列腺液中MIP-2、MIP-1α水平均显著低于对照组同期(P0.01)。两组不良反应发生率对比差异无统计学意义(P0.05)。结论:普适泰联合地奥司明治疗老年CP/CPPS能更安全有效地改善患者的临床症状,可能与其显著降低血清和前列腺液中MIP-2、MIP-1α水平有关。  相似文献   

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Mycobacterium avium is both a pathogen that infects several hosts such as humans, pigs, and birds, as well as a microorganism that is encountered in environmental sources (soil and water). Protein secretion by the bacterium is likely to influence its ability to overcome adverse and competitive conditions both within or outside the host. Using a combination of cloning and information available in the databank, we characterized the secA gene from M. avium, encoding for a major preprotein translocase subunit associated with the secretion system of prokaryotics. In addition, we cloned the secA promoter sequence in a reporter construct upstream of a promoterless gfp. It was determined that the secA of M. avium shares large homology with the secA of Mycobacterium tuberculosis but not with secA of Mycobacterium leprae. secA expression was determined to be greater at logarithmic growth phase although it was also expressed at low levels during the stationary phase. secA expression was also observed when the bacteria were incubated in water as well as within human monocyte-derived macrophages and in conditions that are associated with biofilm formation. Future evaluation of the sec pathway in M. avium might provide important information about secreted proteins that are required for survival in different environments.  相似文献   

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Nitric oxide (NO) reacts with superoxide to produce peroxynitrite, a potent oxidant and reportedly exerts cytotoxic action. Herein we validated the hypothesis that interaction of NO with superoxide exerts protection against superoxide toxicity using macrophages from mice with a knockout (KO) of inducible NO synthase (NOS2) and superoxide dismutase 1 (SOD1), either individually or both. While no difference was observed in viability between wild-type (WT) and NOS2KO macrophages, SOD1KO and SOD1-and NOS2-double knockout (DKO) macrophages were clearly vulnerable and cell death was observed within four days. A lipopolysaccharide (LPS) treatment induced the formation of NOS2, which resulted in NO production in WT and these levels were even higher in SOD1KO macrophages. The viability of the DKO macrophages but not SOD1KO macrophages were decreased by the LPS treatment. Supplementation of NOC18, a NO donor, improved the viability of SOD1KO and DKO macrophages both with and without the LPS treatment. The NOS2 inhibitor nitro-l-arginine methyl ester consistently decreased the viability of LPS-treated SOD1KO macrophages but not WT macrophages. Thus, in spite of the consequent production of peroxynitrite in LPS-stimulated macrophages, the coordinated elevation of NO appears to exert anti-oxidative affects by coping with superoxide cytotoxicity upon conditions of inflammatory stimuli.  相似文献   

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