CD68、CD11c和CD163阳性巨噬细胞在乳腺癌组织中表达及与临床病理特征和预后的关系

目的 探讨乳腺癌肿瘤间质(tumor stroma,TS)中CD68+、CD11c+和CD163+肿瘤相关巨噬细胞(tumor associ-ated macrophages,TAM)的免疫组化表达及与临床病理特征、生存期的关系.方法 采用免疫组化法检测81例乳腺癌和50例乳腺腺病组织中CD68、CD11c和CD163...     

M1和M2型巨噬细胞表型的比较分析

通过对M1和M2型巨噬细胞表型相关指标的比较分析,评价各鉴定巨噬细胞类型的表型指标及其意义。按常规方法以IFN-γ及LPS将骨髓来源巨噬细胞诱导成M1型巨噬细胞,以IL-4诱导出M2型巨噬细胞。分别以RT-PCR和酶活性定量方法检测精氨酸代谢相关酶的表达和活性;以ELISA检测IL-12和IL-10的分泌;以FACS检测巨噬细胞膜分子的表达。结果显示:M1型巨噬细胞诱导性一氧化氮合酶(inducible nitric oxide synthase,iNOS)表达和活性水平较未刺激组明显升高,IL-12产生显著增加,CD16/32表达上调;而M2型巨噬细胞I型精氨酸酶(arginase 1,Arg-1)的表达水平和酶活性较未刺激巨噬细胞显著提高,IL-10分泌轻度增加,并且表达高水平的CD206和DECTIN-1。表型比较分析结果表明,iN-OS表达和活性、IL-12的分泌和膜蛋白CD16/32可用于鉴定M1型巨噬细胞,而Arg-1、CD206和DECTIN-1是鉴定M2型巨噬细胞较为理想的表型指标。     

M2型肿瘤相关巨噬细胞通过p53途径下调肝癌化疗敏感性的机制研究

目的 通过研究M2肿瘤相关巨噬细胞调控p53表达来下调肝癌化疗敏感性的机制,以此拓宽建立抗肿瘤耐药的措施.方法 构建小鼠肝癌模型及分离肝癌组织,研磨组织提取巨噬细胞,通过RT-PCR方法检测巨噬细胞表面CD206及CD163分子表达情况.培养人单核巨噬细胞(THP-1),PMA (100ng/mL)和IL-4 (100ng/mL)作用诱导分化成肿瘤相关巨噬细胞后,与肝癌细胞(HepG2、SMMC7721,Hep 3B)共培养,加入奥沙利铂(20μ g/mL)作用24小时,通过Western blot方法检测凋亡相关蛋白Caspase 3、抗凋亡蛋白Bcl-2及p53的表达,通过MTT方法检测化疗对肝癌细胞增殖情况.结果 成功构建了肝癌模型,分离出了肝癌组织巨噬细胞,RT-PCR检测CD206和CD163的表达显著升高;人单核细胞(THP-1)经加入PMA(100ng/mL)和IL-4 (100ng/mL)分化诱导48h后其细胞的表面CD206和CD163的表达明显高于THP1分化诱导的细胞表面表达量;肝癌细胞SMMC7721和HepG2与M2型肿瘤相关巨噬细胞共培养24h,经奥沙利铂作用后,肿瘤细胞Bcl-2表达明显升高,Caspase 3和p53的表达显著降低;肿瘤细胞的增殖抑制率明显降低,而Hep 3B细胞的凋亡则明显降低.结论 M2型肿瘤相关巨噬细胞调控肝癌细胞中p53的表达,进而抑制了肝癌化疗的敏感性.     

M1/M2型巨噬细胞与心血管疾病关系的研究进展

巨噬细胞是固有免疫的重要组成细胞,参与机体炎症反应、免疫调节、组织修复与重构等过程。巨噬细胞可分为M1型与M2型,前者促进炎症并抑制细胞增殖,后者促进增殖和组织修复。心血管疾病是一类常见的非感染性疾病,研究发现,M1/M2型巨噬细胞通过分泌多种细胞因子和酶类,在高血压、动脉粥样硬化、心肌梗死等的组织损伤与修复中起到重要作用,很大程度上影响着心血管疾病的发展与转归。通过调控M1/M2的平衡,使病理状态得到改善,可能成为治疗心血管疾病的一种新思路。     

癌相关成纤维细胞与M2型巨噬细胞相互作用促进肿瘤发生发展的研究进展

癌相关成纤维细胞(CAF)是肿瘤微环境(TME)中主要成分之一。在TME中,肿瘤细胞与非肿瘤细胞之间或非肿瘤细胞与非肿瘤细胞之间的相互作用能促进肿瘤发生发展。CAF可与多种免疫细胞之间产生相互作用,通过抑制适应性免疫细胞功能,重塑TME中免疫微环境促进肿瘤的发生发展。其中CAF与巨噬细胞相互作用,并诱导巨噬细胞向M2型极化在促进肿瘤发生发展中起到重要作用。     

NT-3促进脂多糖诱导的M1型巨噬细胞向M2表型极化

目的探讨神经营养素-3(NT-3)能否促进脂多糖(LPS)诱导的M1型巨噬细胞向M2型巨噬细胞极化。方法体外培养小鼠RAW264.7巨噬细胞株,分为LPS组和LPS+NT-3组。用脂多糖(100 ng/ml)刺激12h后,撤掉LPS培养基,冲洗,分别加入基础培养基和含有NT-3(40 ng/ml)的基础培养基,培养24 h后,全部置换成基础培养基培养24 h,收集上清与细胞。固定后的细胞分别做CD68/CCR7(M1型细胞标记物)、CD68/CD206(M2型细胞标记物)、CD68/Trk C免疫荧光双标染色。用酶联吸附试验(ELISA)检测上清中TNF-α和IL-10水平。结果免疫荧光细胞化学染色显示,LPS刺激后的巨噬细胞表达NT-3的受体Trk C。LPS组可观察到较多的M1型细胞和较少的M2型细胞。LPS+NT-3组可观察到M1型细胞数减少,而M2型细胞数增多。与LPS组比较,LPS+NT-3组的M1型巨噬细胞比例降低,同时M2型巨噬细胞比例增加(P<0.01)。ELISA结果显示,与LPS组比较,LPS+NT-3组上清中TNF-α的水平明显下降(P<0.01),IL-10的水平相对升高但是差异不明显(P>0.05)。结论 NT-3促进M1型巨噬细胞向M2型极化可能通过与其受体Trk C结合发挥作用,进而减少促炎因子TNF-α的分泌。     

Gpnmb在小鼠M1和M2型骨髓源性巨噬细胞中表达的差异

目的了解小鼠M1和M2型骨髓源性巨噬细胞（ BMMφs）中非转移性黑色素瘤糖蛋白b（ Gpnmb）表达的差异。方法原代培养小鼠BMMφs,免疫荧光染色F4/80和流式细胞仪检测CD11b鉴定巨噬细胞;用IFN-γ和LPS诱导BMMφs向M1型分化,用IL-4诱导向M2型分化。实时荧光定量PCR检测M1型巨噬细胞标志物（ TNF-α、iNOS）、M2型巨噬细胞标志物（ MMR、Arg-1）和Gpn-mb的mRNA表达;免疫荧光双染色、Western印迹、流式细胞仪检测Gpnmb与MMR的蛋白表达。结果（1）免疫荧光染色结果示BMMφs中F4/80高表达;流式细胞仪检测结果示BMMφs中有（92．7±6．1）％细胞表达CD11b,提示BMMφs培养成功;（2）相对于未分化的M0型BMMφs,TNF-α、iNOS mRNA在M1型BMMφs中高表达（P均＜0．01）,而MMR、Arg-1 mRNA在M2型BMMφs中高表达（P均＜0．01）,提示原代M1、M2型BMMφs分化成功;（3）M2型BMMφs 的Gpnmb mRNA和蛋白表达均较M0型和M1型BMMφs显著增高（P均＜0．01）;免疫荧光双染色及流式细胞仪结果显示,BMMφs中Gpnmb与MMR共表达,在M2型BMMφs中MMR阳性BMMφs有（83．2±9．7）％表达Gpnmb。结论 M2型BMMφs的Gpnmb表达较M1型BMMφs显著增高,提示Gpnmb可能作为鉴别M1、M2型巨噬细胞的标志物,在巨噬细胞的表型分化中起作用。     

肿瘤相关巨噬细胞研究进展

单核巨噬细胞是一种多功能细胞,对不同的微环境信号应答表现出不同的功能。而极化的MI和M2巨噬细胞是巨噬细胞功能表现的两个极端。其中侵润到肿瘤组织的巨噬细胞受肿瘤诱导产生的细胞因子的影响使巨噬细胞表现出巨噬细胞M2型表型,这些极化的巨噬细胞在破坏适应性免疫反应和促进肿瘤生长与进展方面具有重要作用。肿瘤相关巨噬细胞（TAM）可以促进肿瘤进展包括促进肿瘤生长、侵润、转移,促进血管生长和免疫抑制等,因而研究TAM具有重要意义。     

肿瘤相关巨噬细胞在皮肤癌中的作用与进展

肿瘤相关巨噬细胞(TAM)是肿瘤微环境中重要的免疫细胞,与肿瘤的发生发展息息相关,TAM不仅可以促进肿瘤细胞的侵袭作用及转移,还可以促进肿瘤血管的生成,以TAM为靶点的肿瘤免疫治疗是目前肿瘤治疗的前沿和研究热点。本文介绍了TAM的极化、转化、与肿瘤发生发展的关系,以及皮肤癌治疗中的进展。     

Linc00514通过调控miR-378a对肝癌巨噬细胞M2型极化的影响北大核心CSCD

目的:探讨Linc00514调节肝癌巨噬细胞M2型极化的作用及分子机制。方法:RT-qPCR检测Linc00514和miR-378a在肝癌患者组织和细胞中的表达。生物信息学软件和双荧光素酶报告基因实验预测和验证Linc00514与miR-378a的相互作用。将Linc00514-siRNA或NC-siRNA及NC inhibitor、miR-378a inhibitor质粒共转染至HepG2细胞。人单核细胞THP-1与转染后的HepG2细胞上清共培养诱导巨噬细胞极化。RT-qPCR和Western blot检测M2型巨噬细胞标志物精氨酸酶-1(Arg-1)、CD163、CD206和M1型巨噬细胞标志物TNF-α、人类白细胞抗原(HLA)-DR mRNA和蛋白水平。结果:肝癌组织和细胞系中,Linc00514表达显著升高,miR-378a表达显著降低(P<0.05)。肝癌组织中M2型巨噬细胞标志物Arg-1、CD163、CD206 mRNA表达显著升高(P<0.05)。Linc00514靶向负调控miR-378a表达。沉默Linc00514显著抑制Arg-1、CD163和CD206 mRNA和蛋白表达,促进M1型巨噬细胞标志物TNF-α和HLA-DR mRNA和蛋白表达(P<0.05)。抑制miR-378a显著逆转Linc00514对巨噬细胞极化的作用。结论:沉默Linc00514通过靶向miR-378a抑制肝癌巨噬细胞M2型极化。     

The macrophage scavenger receptor CD163

Mature tissue macrophages form a first line of defense to recognize and eliminate potential pathogens; these specialized cells are capable of phagocytosis, degradation of self and foreign materials, establishment of cell-cell interactions, and the production of inflammatory mediators. Mature tissue macrophages express a variety of receptors, including the scavenger receptor cystein-rich (SRCR) superfamily members. CD163 is a member of the SRCR family class B and is expressed on most subpopulations of mature tissue macrophages. The best characterized function of CD163, which is essentially a homeostatic one, is related to the binding of Hemoglobin:Haptoglobin complexes. Furthermore, it has been suggested that CD163 positive macrophages or the soluble form of CD163 plays a role in the resolution of inflammation, as they are found in high numbers in inflamed tissue.     

Increased serum levels of macrophage activation marker sCD163 in Dengue patients

BackgroundDengue viruses are known to infect and replicate in macrophages. Thus studying the host responsive molecules that are specifically released by macrophages during the course of dengue infection may provide better understanding on dengue immunopathogenesis. Soluble CD163 (sCD163) is a scavenger receptor, highly expressed on macrophages reported to be involved in some viral disease. The participation of sCD163 in dengue is not known.ObjectiveThe present study aimed to explore the role of sCD163 as a potential biomarker for predicting dengue disease.Study designUsing a case-control design, 82 dengue subjects consisting of 69 non-severe dengue (NSD) and 13 severe dengue (SD) along with 32 non-dengue other febrile illness (OFI) subjects and 30 healthy subjects were involved in the study. The serum concentration of sCD163 was determined in the study subjects at admission and around defervescence using ELISA. Statistical analysis was done using Mann-Whitney U test andWilcoxon signed rank test.ResultsThe study recorded a significant increase in the sCD163 serum level at defervescence phase specifically among dengue group compared to OFI. sCD163 was also found to be significantly higher in secondary cases compared to primary at both admission and defervescence. Furthermore,a higher level of sCD163 was also observed in SD compared to NSD cases, although no statistical significance was observedConclusionThe study substantiates the role of macrophage activation in dengue pathogenesis and further study is needed to decipher the exact role of sCD163 in the disease pathogenesis and to explore its potential as a marker for the early prediction of dengue severity.     

CD163: a specific marker of macrophages in paraffin-embedded tissue samples

Paraffin-section immunohistochemical analysis was performed using a monoclonal antibody against CD163 to evaluate the antibody's usefulness in identifying cells of monocyte/macrophage lineage in normal and neoplastic conditions. Normal human tissue samples and samples from 211 hematopoietic disorders and 115 nonhematopoietic neoplasms were examined. The distribution of KP1 and PG-M1, monoclonal antibodies to the macrophage-associated CD68 antigen, also were evaluated for comparison. CD163 immunoreactivity was observed in resident macrophages of all normal tissue samples except splenic white pulp macrophages and germinal center tingible body macrophages. Among hematopoietic disorders and nonhematopoietic neoplasms, CD163 expression was restricted largely to cases of chronic myelomonocytic leukemia, histiocytic sarcoma, sinus histiocytosis with massive lymphadenopathy, and littoral cell angioma. Acute myeloid leukemias (AMLs) with monocytic differentiation were CD163- with the exception of 1 case of acute monoblastic leukemia. Most myeloid sarcomas also were CD163-. Compared with the CD68 antibodies, CD163 demonstrated greater specificity as a marker of disorders of monocyte/macrophage origin. However, immunohistochemical evaluation of CD163 expression does not seem to be a sensitive means of determining monocytic differentiation in AMLs in paraffin sections or establishing a diagnosis of myeloid sarcoma.     

肝癌相关肿瘤标志物研究新进展

肝细胞癌( hepatocellular carcinoma, HCC )是常见的恶性肿瘤之一,其发病隐匿,恶性程度高,病死率高,因此早期诊断对于提高患者的生存率至关重要.目前临床上主要运用甲胎蛋白(alpha-fetoprotein, AFP )结合影像学及病理学检查进行肝癌的早期诊断;但是AFP对于肝癌筛查的特异性...     

HHLA2 在恶性肿瘤中的研究进展

近年来,随着对肿瘤发病机制的深入研究,免疫治疗已取得突破性进展,以程序性死亡分子1(PD-1) / 程序性死亡分子配体1(PD-L1)为代表的Pembrolizumab 和Nivolumab 等药物已被批准用于临床。而人内源性逆转录病毒-H 长末端重复关联蛋白2 (HHLA2)与PD-L1 均为B7 家族成员,具有同源性,在多种实体恶性肿瘤中均呈高表达,极有可能成为继PD-L1 后的又一重要免疫检查和治疗靶点。现就HHLA2 在恶性肿瘤中的研究进展做一综述。     

以糖蛋白类肿瘤标志物为靶向的嵌合抗原受体修饰T细胞研究进展

嵌合抗原受体(chimericantigenreceptor,CAR)修饰T细胞是目前肿瘤治疗中新的靶向疗法,通过单链抗体(singlechainfragmentvariable,scFv)-共刺激分子-T细胞信号转导区构成的嵌合模式修饰T细胞,赋予T细胞非MHC依赖性靶向杀伤肿瘤细胞的能力,在动物模型及临床试验中取得了良好的效果.糖蛋白类肿瘤标志物由于其良好的靶向性成为了CAR修饰T细胞新的靶点,针对糖蛋白类肿瘤标志物的靶向研究显示出良好的临床前景,但是也考虑到脱靶效应,转染方式等问题对该治疗在临床运用的限制.相信随着研究的逐渐深入,基于CAR修饰T细胞的糖蛋白类肿瘤标志物靶向治疗会取得更大的突破.     

Histiocytic sarcoma: a study of five cases including the histiocyte marker CD163.

Histiocytic sarcoma (HS) is a rare but controversial hematopoietic neoplasm. In the past, malignancies have been misclassified as histiocytic tumors due to overlapping histologic features and inadequate phenotypic data. CD163, a recently characterized hemoglobin scavenger receptor, appears to be a 'specific' marker of histiocytic lineage and a promising diagnostic tool for evaluating histiocytic neoplasms. Five cases of HS were studied to further elucidate the clinicopathologic features of these rare tumors and to demonstrate the diagnostic utility of CD163. Criteria for diagnosis included histologic and immunohistochemical evidence of histiocytic differentiation, CD45 positivity, and exclusion of lymphoid, epithelial, melanocytic and dendritic cell phenotype. Sites of disease included the colon (two cases), palate, inguinal lymph node, and testis. The clinical course was aggressive in 4/5 patients (survival=2-15 months). One patient with localized disease of the palate, survived 17 years after diagnosis. All patients with poor survival had tumors > or =3.5 cm. Histologically, all cases showed diffuse architecture with large, discohesive polygonal cells. Spindling of cells was focally noted. Hemophagocytosis was identified in 3/5 cases. A prominent inflammatory background was present in 4/5 tumors. All cases were immunoreactive for CD45, CD163, CD68, and lysozyme. S-100 was focally positive in 4/5 cases. Antibodies for melanocytic, epithelial, lymphoid, and dendritic cell markers were negative. Molecular studies showed monoclonal IgH gene rearrangements in three cases. Our findings suggest that HS is an uncommon neoplasm frequently extranodal in presentation and aggressive in behavior, with rare exceptions. Stage of disease and possibly tumor size are significant prognostic indicators. Molecular studies remain controversial in the diagnosis. The morphologic and phenotypic features are relatively uniform; however, the diagnosis requires exclusion of more common neoplasms by extensive immunophenotypic studies. CD163 appears to be a specific histiocytic marker and is important in establishing the diagnosis of HS.