鱼类CXC型趋化因子受体研究进展

鲤鱼是我国主要养殖鱼类之一,但其病害较多。作为机体免疫的重要组成部分,鲤鱼趋化因子受体日益受到研究者的重视,趋化因子受体在机体的免疫系统中发挥重要的作用。对其充分的研究有利于更深入地了解机体的免疫应答的分子机制,为研究物种进化和鱼类疾病的防治提供重要的线索。本文着重对鱼类趋化因子受体的分子克隆、组织表达和生物学功能作一综述。     

43例妊娠妇女血清贫血检测指标的分析

检测了血清铁（SerumIron）、铁蛋白（Ferritin）和可溶性转铁蛋白受体（Soluble transferrin receptor,sTfe）等指标,并分析了这些指标在诊断妊娠妇女缺铁性贫血中的临床意义。采用免疫分析法和比色法测定43例妊娠24—28周妇女和同期收集的30例健康妇女的血清铁、铁蛋白和可溶性转铁蛋白受体的水平,利用SPSS10．0软件对实验数据进行统计学分析。妊娠组血清铁、可溶性转铁蛋白受体均值较正常对照组无显著差异,铁蛋白均值为19．62±11．52ng／L,明显低于对照组61．14±39．92ng／L（P〈0．05）。按血红蛋白浓度的高低分为4组：1组为Hb〈100g／L,2组为Hb100～110g／L,3组为Hb110—120g／L,4组为Hb〉120s／L。1组只有铁蛋白与对照组有显著差别（P〈0．05）,2组铁蛋白、VitB13和转铁蛋白受体与对照组均有显著差别（P〈0．05）,3组和4组铁蛋白和VitB13与对照组有显著差别（P〈0．05）。在诊断妊娠妇女缺铁性贫血中,铁蛋白是估计人体铁状态的最好参数,可溶性转铁蛋白受体测定在怀孕期间没有显著变化,如有功能性铁缺乏会出现sTfe浓度升高。而血清铁是检测缺铁及铁负荷过多疾病的有效指标,但在一定时期内表现不明显,变化不大。     

武术套路运动对大学生免疫功能的影响研究

通过观察42名大学生不同强度武术套路锻炼前后免疫细胞数量及机体血清中免疫球蛋自水平的变化。结果表明：经过16周中等强度的武术套路锻炼，能改善、提高机体的细胞免疫和体液免疫水平，对增强体质、防治疾病具有重要作用。     

创伤对家兔血清胰岛素及铜,铁,锌含量的影响

创伤可引起强烈的应激反应，造成机体的内分泌代谢紊乱。本研究测定了围创伤期家兔胰岛素水平及血清铜、铁、锌含量，结果创伤后出现了明显的胰岛素抵抗，且创伤后血清铜、铁、锌浓度下降。创伤可引起机体强烈的应激反应，造成机体内分泌和代谢的紊乱，进而破坏内环境的稳定［１］。本研究拟对１５只家兔造成开胸创伤，观察围创伤期胰岛素水平以及血清铜、铁、锌含量的变化。     

微血管密度与血管内皮生长因子受体-3在骨髓增生异常综合征患者中的表达及意义

目的检测骨髓增生异常综合征患者骨髓中微血管密度和血管内皮生长因子受体-3表达水平并探讨其临床意义。方法采用免疫组织化学染色检测54例骨髓增生异常综合症患者、20例非恶性血液病患者对照组骨髓组织中微血管密度和血管内皮生长因子受体-3表达水平,采用蛋白质印迹法检测上述研究对象骨髓单个核细胞中血管内皮生长因子受体-3蛋白表达水平,分析其与临床特征的相关性。结果骨髓增生异常综合症患者骨髓组织中微血管密度和血管内皮生长因子受体-3表达水平明显高于非恶性血液病对照组,差异具有统计学意义(P0.05),而骨髓增生异常综合症低危组、中危组及高危组中微血管密度与血管内皮生长因子受体-3的表达水平无显著差异(P0.05),经相关性分析微血管密度和血管内皮生长因子受体-3在骨髓增生异常综合症患者骨髓中表达呈正相关关系。结论骨髓增生异常综合症患者骨髓存在明显血管新生及血管内皮生长因子受体-3高表达,其表达水平可能参与骨髓增生异常综合症发病、发展等过程,并可能影响骨髓增生异常综合症预后,通过检测微血管密度和血管内皮生长因子受体-3的表达可为临床抗脉管新生方法治疗骨髓增生异常综合症提供实验依据。     

NK细胞免疫识别及其调节机制与免疫相关性疾病

自然杀伤受体(NKR)和Toll样受体(TLR)是天然免疫系统最重要的二群天然免疫识别受体家族,位于机体抵抗外来侵袭的第一道防线.二者各自具有独特的识别外来或内源性的危险信号、区分自我和非我的识别机制,是启动固有免疫和适应性免疫应答的关键链接分子.NK细胞是天然免疫系统的核心成员,具有早期识别和清除病毒感染和肿瘤细胞等功能,同时也是连接天然免疫和获得性免疫的桥梁.以NK细胞为载体将TLRs/NKRs连接起来,可以较好地反映机体内外环境变化或刺激时固有免疫对适应性免疫的调节作用,为有效控制感染、炎症、肿瘤及自身免疫性疾病提供崭新的治疗策略.     

TNF-α、INF-γ和EPO与肿瘤伴ACD造血功能低下的相关性

目的:探讨肿瘤坏死因子α(TNF-α)、干扰素γ(INF-γ)和红细胞生成素(EPO)对肿瘤伴慢性病贫血(ACD)造血功能的影响.方法:检测肿瘤患者铁代谢参数;ELISA法检测患者血清TNF-α、IFN-γ和EPO水平;观察3种细胞因子及患者血清对骨髓红系集落生成单位(CFU-E)生成的影响.结果:肿瘤伴ACD患者血清EPO水平高于正常对照,而低于IDA患者;血清TNF-α、IFN-γ水平显著升高,且与血球压积、血清铁水平负相关;TNF-α、IFN-γ可抑制正常骨髓CFU-E生成,患者血清可抑制自身骨髓CFU-E生成,rhEPO可部分纠正细胞因子对CFU-E的抑制.结论:TNF-α、IFN-γ和EPO与肿瘤伴ACD造血功能低下有关.     

运动对骨形态发生蛋白6介导的机体铁代谢调节机制的研究进展

骨形态发生蛋白6(BMP6)为TGF-β超家族中一员,它产生于骨髓源性间质干细胞(BMSC)及造血干细胞,是一种调节成骨细胞和成软骨细胞分化的骨生长因子,在骨缺损的修复中具有重要作用.运动可促进BMP6的表达.研究发现,BMP6也是铁调素的重要的内源调节子,可以上调铁调素的表达,而铁调素是肠铁吸收的负调节子.因此,运动引起的BMP6表达增加,可以促进机体铁的吸收和释放,从而对运动中维持机体铁的动态平衡有重要的调控作用.     

E玫瑰花结形成试验对病毒性肝炎患者免疫状态测定的初步观察

机体的免疫反应,主要是依靠免疫活性细胞来实现的。人类免疫活性细胞分胸腺依赖淋巴细胞(Thymus—Dependent lymphocytes 简称 T 淋巴细胞)和骨髓衍生细胞(Bone marrow—derived Lymphocytes 简称 B 淋巴细胞)。两者同时存在于周围淋巴样组织及外周     

免疫重建

免疫重建Ｉｍｍｕｎｏｒｅｃｏｎｓｔｉｔｕｔｉｏｎ￥／／谢蜀生（北京医科大学免疫学教研室，教授北京１０００８３）机体丧失功能的病变器官可以通过器官移植重建其生理功能。骨髓是一切血细胞和兔疫细胞的来源，骨髓移植（ＢＭＴ）不但可以治疗先天、后天造血与免疫缺...     

Crystal structure of the hereditary haemochromatosis protein HFE complexed with transferrin receptor

HFE is related to major histocompatibility complex (MHC) class I proteins and is mutated in the iron-overload disease hereditary haemochromatosis. HFE binds to the transferrin receptor (TfR), a receptor by which cells acquire iron-loaded transferrin. The 2.8 A crystal structure of a complex between the extracellular portions of HFE and TfR shows two HFE molecules which grasp each side of a twofold symmetric TfR dimer. On a cell membrane containing both proteins, HFE would 'lie down' parallel to the membrane, such that the HFE helices that delineate the counterpart of the MHC peptide-binding groove make extensive contacts with helices in the TfR dimerization domain. The structures of TfR alone and complexed with HFE differ in their domain arrangement and dimer interfaces, providing a mechanism for communicating binding events between TfR chains. The HFE-TfR complex suggests a binding site for transferrin on TfR and sheds light upon the function of HFE in regulating iron homeostasis.     

Transferrin receptor 1 is a cellular receptor for New World haemorrhagic fever arenaviruses

At least five arenaviruses cause viral haemorrhagic fevers in humans. Lassa virus, an Old World arenavirus, uses the cellular receptor alpha-dystroglycan to infect cells. Machupo, Guanarito, Junin and Sabia viruses are New World haemorrhagic fever viruses that do not use alpha-dystroglycan. Here we show a specific, high-affinity association between transferrin receptor 1 (TfR1) and the entry glycoprotein (GP) of Machupo virus. Expression of human TfR1, but not human transferrin receptor 2, in hamster cell lines markedly enhanced the infection of viruses pseudotyped with the GP of Machupo, Guanarito and Junin viruses, but not with those of Lassa or lymphocytic choriomeningitis viruses. An anti-TfR1 antibody efficiently inhibited the replication of Machupo, Guanarito, Junin and Sabia viruses, but not that of Lassa virus. Iron depletion of culture medium enhanced, and iron supplementation decreased, the efficiency of infection by Junin and Machupo but not Lassa pseudoviruses. These data indicate that TfR1 is a cellular receptor for New World haemorrhagic fever arenaviruses.     

常见肝癌细胞系的转铁蛋白受体表达差异分析及主动靶向载体效率比较

转铁蛋白受体1(transferrin receptor 1,TfR1)可介导细胞内吞过程,从而摄取与之特异结合的纳米颗粒,因此成为许多主动靶向型纳米载体的靶点。研究表明,肝癌细胞存在TfR1高表达现象,可作为肿瘤治疗纳米药物递送系统的关键性靶点。体外评价是TfR1靶向纳米载体的重要研究环节,然而肝癌细胞模型种类繁多,其TfR1表达水平可能存在一定差异。选择了几种常见的肝癌细胞系,包括HepG2、Hep3B、MHCC97-H以及Huh-1,分别从mRNA水平以及蛋白水平测定了细胞系TfR1的表达情况,考察了转铁蛋白(Tf)以及转铁蛋白核酸适配体(transferrin nucleic acid aptamer, Tf-APT)对不同细胞的亲和效率。同时,制备了包载紫杉醇的TfR1靶向脂质体,并考察其对不同细胞系的细胞生长抑制作用。结果表明,4种肝癌细胞系在mRNA水平以及蛋白水平均存在TfR1的表达差异;同时,体外抗肿瘤结果显示,不同肝癌细胞系对紫杉醇-TfR1靶向脂质体的敏感性也存在显著不同。     

A protein on Plasmodium falciparum-infected erythrocytes functions as a transferrin receptor

Several observations suggest that iron is essential for the development of malaria parasites but there is evidence that the parasites in erythrocytes do not obtain iron from haemoglobin. The total haemin level in parasitized erythrocytes does not vary during parasite development, indicating that the iron-containing moiety of haemoglobin is not detectably metabolized. Although parasite proteases can degrade the protein part of haemoglobin in red cells, no parasite enzymes that degrade haemin have been identified. In mammalian cells, haemin is degraded to carbon monoxide and bilirubin by the enzyme haeme oxygenase. This enzyme has not been found in malaria parasites. In fact haemin has been found to be toxic to parasite carbohydrate metabolism. Thus, iron apparently cannot be liberated from haemin and instead is sequestered in infected red cells as haemozoin, the characteristic pigment associated with malarial infection. If iron bound to transferrin is the source of ferric ions for malaria parasites within mature erythrocytes, then the parasite must synthesize its own transferrin receptor and localize it on the surface of the infected cell, because the receptors for transferrin are lost during erythrocyte maturation. Our results here suggest that Plasmodium falciparum synthesizes its own transferrin receptors enabling it to take up iron from transferrin by receptor-mediated endocytosis.     

Selection and properties of a mouse L-cell transformant expressing human transferrin receptor

Transferrin receptors are expressed in large quantities on tissues with high requirements for iron such as maturing erythroid cells and placenta. In addition, they are found in abundance on proliferating cells from other normal tissues as well as on a variety of tumours. Recent genetic analysis has shown that structural genes for the transferrin receptor, probably transferrin itself and for p97, a melanoma-associated antigen that exhibits primary sequence homology with transferrin and that can bind ferric iron, each map in man to chromosome 3 (refs 9-12). On this basis it has been suggested that there may be a region on chromosome 3 containing genes involved in Fe transport and that rearrangements in this region of chromosome 3 may in some circumstances be associated with malignant transformation. Furthermore, it is unresolved whether all cell types express structurally identical transferrin receptors. To study these problems, and as an initial step towards cloning the transferrin receptor gene, we describe here the derivation of mouse L-cell transformants expressing the human transferrin receptor.     

淡水养殖鱼类血清转铁蛋白耐低氧特性的研究

用聚丙烯酰胺凝胶电泳、含铁蛋白质专一染色法及利凡诺 ( Rivanol)溶液沉淀法确定了鲤鱼、鲫鱼等 1 2种淡水养殖鱼的血清转铁蛋白在聚丙烯酰胺凝胶中的位置 ,鉴定出 8类鲤鱼、6类鲫鱼和 3类白鲢的血清转铁蛋白的特异类型 ,并分析了转铁蛋白多态体的表现型和基因型 .测定了鲤鱼、鲫鱼、白鲢和鳙鱼的血清铁浓度、铁结合能力及铁饱和度 .通过分析淡水养殖鱼类耗氧量及窒息点临界含氧量与血清转铁蛋白的关系 ,证实了鱼类转铁蛋白具有耐低氧的特性 .     

细菌的铁供给研究

在大多数生物机体中，Fe^3 的获得都有着特殊的机制．细菌利用载铁颗粒、铁血红素、血红蛋白来运输铁，并且受基因表达的调控．     

Apolactoferrin structure demonstrates ligand-induced conformational change in transferrins

Proteins of the transferrin family, which contains serum transferrin and lactoferrin, control iron levels in higher animals through their very tight (Kapp approximately 10(20)) but reversible binding of iron. These bilobate molecules have two binding sites, one per lobe, each housing one Fe3+ and the synergistic CO3(2-) ion. Crystallographic studies of human lactoferrin and rabbit serum transferrin in their iron-bound forms have characterized their binding sites and protein structure. Physical studies show that a substantial conformational change accompanies iron binding and release. We have addressed this phenomenon through crystal structure analysis of human apolactoferrin at 2.8 A resolution. In this structure the N-lobe binding cleft is wide open, following a domain rotation of 53 degrees, mediated by the pivoting of two helices and flexing of two interdomain polypeptide strands. Remarkably, the C-lobe cleft is closed, but unliganded. These observations have implications for transferrin function and for binding proteins in general.     

结核分枝杆菌对感染小鼠肺泡巨噬细胞转铁蛋白受体和铁蛋白表达的影响

探讨不同毒力结核分枝杆菌感染对小鼠肺泡巨噬细胞转铁蛋白受体(TfR)和铁蛋白(Fn)表达的影响及其时相性变化。利用制备的卡介苗(以下简称BCG)和结核分枝杆菌国际标准强毒株H37Rv株(以下简称H37Rv株)悬液,分别经小鼠尾静脉注射,建立各组小鼠感染模型,各组小鼠感染模型建立成功后,分别于第1、3、5、7、9、11、13、15天,进行各组小鼠肺泡灌洗,收集小鼠肺泡灌洗液,获取各组小鼠肺泡巨噬细胞。应用ELISA方法和Western blot技术检测各组小鼠肺泡巨噬细胞TfR和Fn的表达。利用ELISA方法检测各组小鼠肺泡巨噬细胞TfR的表达结果显示:H37RV组与BCG组小鼠肺泡巨噬细胞TfR表达均高于空白对照组,在感染第7、9、11天差异最明显,具有统计学意义(P0.05)。利用Western blot技术检测各组小鼠肺泡巨噬细胞TfR表达结果显示:于模型建成后第7、9、11天,H37RN组、BCG组、空白对照组三组之间差异有统计学意义(P0.05)。用ELISA方法和Western blot技术检测各组小鼠肺泡巨噬细胞内Fn表达结果显示:于模型建成后第7、9、11天,H37RV组与BCG组的小鼠肺泡巨噬细胞内Fn表达量明显减低,并且于第7天时表达量最第,异有统计学意义(P0.05)。结核分枝杆菌感染小鼠,导致小鼠肺泡巨噬细胞TfR的表达增高,而Fn的表达降低。不同毒力的结核杆菌感染后Fn蛋白表达差异并不明显,而不同毒力的结核杆菌感染后TfR蛋白的表达有差异性。