• 【白介素-1α诱导的黑色素瘤细胞运动的特征:I型和II型受体阻断性单克隆抗体的抑制作用。】 复制标题 收藏 收藏
    DOI:10.1097/00008390-199706000-00006 复制DOI
    作者列表:Dekker SK,Vink J,Bruijn JA,Mihm MC Jr,Vermeer BJ,Byers HR
    BACKGROUND & AIMS: Interleukin-1 alpha (IL-1 alpha) induces cell motility in a variety of benign cell types and in some but not all malignant cell lines in vitro. This study characterizes the IL-1 alpha-induced motility of an aggressive human melanoma cell line that expresses both type I and type II IL-1 receptors. We tested the effect of monoclonal antibodies including function-blocking moAbs against the type I and type II IL-1 receptors on melanoma cell motility to determine which receptor is involved in signal transduction of IL-1 alpha-induced melanoma cell motility. IL-1 alpha significantly increases MM-RU melanoma cell migration in a dose-dependent manner using modified Boyden chamber assays at concentrations 10 to 100 times less than concentrations that significantly inhibit cell growth. Computer-assisted time-lapse image analysis reveals that the motility is inhibited in a dose-dependent manner by neutralizing antibodies against IL-1 alpha. Function-blocking monoclonal antibodies against either type I or type II IL-1 receptors show a significant inhibition of cytokine-induced enhanced cell migration. When both the anti-IL-1 receptor antibodies are added together, the motility-response is completely blocked to control levels. Taken together the data indicate that the IL-1 alpha-induced motility of MM-RU melanoma cells is mediated through both type I and type II IL-1 receptors. The significant inhibition of motility by neutralizing IL-1 alpha or blocking either one or both of the IL-1 receptors indicates an integration of IL-1-induced signals in the induction of melanoma cell migration.

    背景与目标: 白细胞介素-1(IL-1 alpha)在多种良性细胞类型中以及某些但不是全部恶性细胞系中诱导细胞运动。这项研究的特点是表达I型和II型IL-1受体的侵略性人黑素瘤细胞系的IL-1α诱导的运动。我们测试了包括针对I型和II型IL-1受体的功能阻断性单抗的单克隆抗体对黑素瘤细胞运动的影响,以确定哪个受体参与了IL-1α诱导的黑素瘤细胞运动的信号转导。 IL-1α使用改良的Boyden室测定法以剂量依赖性方式显着增加MM-RU黑色素瘤细胞迁移,其浓度比明显抑制细胞生长的浓度低10至100倍。计算机辅助的延时图像分析表明,通过中和针对IL-1α的抗体,可以以剂量依赖性的方式抑制运动性。针对I型或II型IL-1受体的功能阻断性单克隆抗体显示出对细胞因子诱导的细胞迁移增强的显着抑制作用。当两种抗IL-1受体抗体一起添加时,运动反应完全被阻断至对照水平。数据合计表明,IL-1α诱导的MM-RU黑色素瘤细胞的运动是通过I型和II型IL-1受体介导的。通过中和IL-1α或阻断任何一个IL-1受体或两个IL-1受体来显着抑制运动性,这表明在黑素瘤细胞迁移的诱导中整合了IL-1诱导的信号。

  • 【抗氧化剂对核因子-κB的抑制作用增强了紫杉醇在卵巢癌细胞系中的敏感性。】 复制标题 收藏 收藏
    DOI:10.1111/j.1525-1438.2006.00652.x 复制DOI
    作者列表:Liu GH,Wang SR,Wang B,Kong BH
    BACKGROUND & AIMS: :The objective of this study was to determine whether paclitaxel and a strong antioxidant, pyrrolidinedithiocarbamate (PDTC), can affect the activation of nuclear factor-kappa B (NF-kappaB) in SKOV-3 human ovarian cancer cell line and the effect of these two agents on the growth and apoptosis of the cancer cells. The cells were treated with various concentrations of paclitaxel and/or PDTC at various time intervals. Following treatments, cell growth and apoptosis were determined by 2-(2-methoxy-4-nitrophenyl)-3-(4-nitrophenyl)-5-(2,4-disulphonyl)-2H-tetrazolium (WST-8) (WST) assay and flow cytometry, respectively. Western blot assay was used to determine the nuclear p65 protein and cytoplasmic IkappaB-alpha protein. High doses of PDTC significantly inhibited the growth of SKOV-3 cells and caused apoptosis. Paclitaxel and lower doses of PDTC combined demonstrated additive inhibition of cell growth and increased levels of apoptosis. Treatment of paclitaxel alone showed increased nuclear p65 protein and decreased cytoplasmic IkappaB-alpha protein expression, while pretreatment of PDTC reversed this function. PDTC blocks the paclitaxel-induced activation of NF-kappaB leading to increased chemosensitivity to paclitaxel and enhanced apoptosis. Combining antioxidants and paclitaxel has significant potential to overcome the risk of paclitaxel resistance.
    背景与目标: :这项研究的目的是确定紫杉醇和强抗氧化剂吡咯烷二硫代氨基甲酸酯(PDTC)是否会影响SKOV-3人卵巢癌细胞系中核因子-κB(NF-kappaB)的活化及其作用两种药剂对癌细胞的生长和凋亡都有影响。在不同的时间间隔用不同浓度的紫杉醇和/或PDTC处理细胞。处理后,通过2-(2-甲氧基-4-硝基苯基)-3-(4-硝基苯基)-5-(2,4-二磺酰基)-2H-四唑鎓(WST-8)(WST)测定细胞生长和凋亡)分析和流式细胞术。蛋白质印迹法用于确定核p65蛋白和细胞质IkappaB-alpha蛋白。高剂量的PDTC显着抑制SKOV-3细胞的生长并引起细胞凋亡。紫杉醇和较低剂量的PDTC联合显示可抑制细胞生长和增加细胞凋亡水平。单独使用紫杉醇的治疗显示核p65蛋白增加,而细胞质IkappaB-α蛋白表达降低,而PDTC的预处理逆转了该功能。 PDTC阻止紫杉醇诱导的NF-κB活化,从而导致对紫杉醇的化学敏感性增加和细胞凋亡增强。抗氧化剂和紫杉醇的组合具有克服紫杉醇耐药性的巨大潜力。
  • 【鸡原始生殖细胞ESTs的基因表达谱。】 复制标题 收藏 收藏
    DOI:10.1186/1471-2164-7-220 复制DOI
    作者列表:Han JY,Park TS,Kim JN,Kim MA,Lim D,Lim JM,Kim H
    BACKGROUND & AIMS: BACKGROUND:Germ cells are the only cell type that can penetrate from one generation to next generation. At the early embryonic developmental stages, germ cells originally stem from primordial germ cells, and finally differentiate into functional gametes, sperm in male or oocyte in female, after sexual maturity. This study was conducted to investigate a large-scale expressed sequence tag (EST) analysis in chicken PGCs and compare the expression of the PGC ESTs with that of embryonic gonad. RESULTS:We constructed 10,851 ESTs from a chicken cDNA library of a collection of highly separated embryonic PGCs. After chimeric and problematic sequences were filtered out using the chicken genomic sequences, there were 5,093 resulting unique sequences consisting of 156 contigs and 4,937 singlets. Pearson chi-square tests of gene ontology terms in the 2nd level between PGC and embryonic gonad set showed no significance. However, digital gene expression profiling using the Audic's test showed that there were 2 genes expressed significantly with higher number of transcripts in PGCs compared with the embryonic gonads set. On the other hand, 17 genes in embryonic gonads were up-regulated higher than those in the PGC set. CONCLUSION:Our results in this study contribute to knowledge of mining novel transcripts and genes involved in germline cell proliferation and differentiation at the early embryonic stages.
    背景与目标: 背景:生殖细胞是唯一可以从一代渗透到下一代的细胞类型。在胚胎发育的早期阶段,生殖细胞最初起源于原始生殖细胞,并在性成熟后分化为功能性配子,雄性精子或雌性卵母细胞。进行这项研究以调查鸡PGC中的大规模表达序列标签(EST)分析,并将PGC EST与胚胎性腺的表达进行比较。
    结果:我们从鸡的高度分离的胚胎PGC的cDNA文库中构建了10,851个EST。使用鸡基因组序列过滤掉嵌合和有问题的序列后,共有5,093个得到的独特序列,由156个重叠群和4,937个单重态组成。 PGC和胚胎性腺集之间第二级的基因本体项的皮尔逊卡方检验没有意义。但是,使用Audic's测试进行的数字基因表达谱分析显示,与胚胎性腺相比,PGC中有2个基因表达显着,且转录本数量更高。另一方面,胚胎性腺中的17个基因上调的程度高于PGC中的基因。
    结论:我们在这项研究中的结果有助于了解在胚胎早期阶段涉及生殖细胞增殖和分化的新转录本和基因。
  • 【巨噬细胞对NF-κB活化的抑制作用减少了泡沫细胞的形成。】 复制标题 收藏 收藏
    DOI:10.1016/j.atherosclerosis.2006.07.018 复制DOI
    作者列表:Ferreira V,van Dijk KW,Groen AK,Vos RM,van der Kaa J,Gijbels MJ,Havekes LM,Pannekoek H
    BACKGROUND & AIMS: :Accumulation of lipid-laden macrophages is a hallmark of atherosclerosis. The relevance of the key transcription factor nuclear factor kappaB (NF-kappaB) for macrophage-derived foam-cell formation has not been unequivocally resolved. Transgenic mice lines were generated in which NF-kappaB activation is specifically inhibited in macrophages by overexpressing a trans-dominant, non-degradable form of IkappaBalpha (IkappaBalpha (32A/36A)) under control of the macrophage-specific SR-A promoter. Alanine substitution of serines 32 and 36 prevents degradation and retains the inactive NF-kappaB/IkappaBalpha (32A/36A) complex in the cytoplasm. Similarly, stable human THP1 monocytic cell lines were generated with integrated copies of IkappaBalpha (32A/36A) cDNA. Upon treatment with oxidized low-density lipoprotein (ox-LDL), murine peritoneal macrophages from transgenic IkappaBalpha (32A/36A) mice, as well as THP1/IkappaBalpha (32A/36A) clones, display decreased lipid loading after differentiation into macrophages. This is accompanied by increased expression of the transcription factors PPARgamma and LXRalpha as well as of the major cholesterol-efflux transporter ABCA1. Paradoxically, mRNA expression of the 'lipid-uptake' receptor CD36 is also increased. Since the net result of these changes is reduction of foam-cell formation, it is proposed that under specific inhibition of NF-kappaB activation, ABCA1-mediated cholesterol efflux prevails over CD36-mediated lipid influx.
    背景与目标: :富含脂质的巨噬细胞的积累是动脉粥样硬化的标志。尚未明确解决关键转录因子核因子κB(NF-κB)与巨噬细胞衍生的泡沫细胞形成的相关性。通过在巨噬细胞特异性SR-A启动子的控制下过表达不可表达形式的IkappaBalpha(IkappaBalpha(32A / 36A)),从而在巨噬细胞中特异性抑制NF-κB活化的转基因小鼠品系。丝氨酸32和36的丙氨酸取代防止降解并在细胞质中保留无活性的NF-κB/IκBα(32A / 36A)复合物。类似地,用整合的IkappaBalpha(32A / 36A)cDNA拷贝产生稳定的人THP1单核细胞系。经氧化低密度脂蛋白(ox-LDL)处理后,转基因IkappaBalpha(32A / 36A)小鼠以及THP1 / IkappaBalpha(32A / 36A)克隆的小鼠腹膜巨噬细胞在分化为巨噬细胞后显示出降低的脂质负载。这伴随着转录因子PPARgamma和LXRalpha以及主要胆固醇外流转运蛋白ABCA1表达的增加。矛盾的是,“脂质摄取”受体CD36的mRNA表达也增加了。由于这些变化的最终结果是减少了泡沫细胞的形成,因此建议在特定抑制NF-κB活化的情况下,ABCA1介导的胆固醇外排比CD36介导的脂质内流更为普遍。
  • 【所谓的“次要” ABO不相容外周血干细胞同种异体移植后的早期致命性免疫溶血。】 复制标题 收藏 收藏
    DOI:10.1038/sj.bmt.1700794 复制DOI
    作者列表:Oziel-Taieb S,Faucher-Barbey C,Chabannon C,Ladaique P,Saux P,Gouin F,Gastaut JA,Maraninchi D,Blaise D
    BACKGROUND & AIMS: A 38-year-old man, blood group A+, was allotransplanted for multiple myeloma from his fully matched sister, blood group O+. Anti-A antibodies IgG and IgM titres of the donor were low. Allogeneic peripheral blood stem cells were harvested by leukapheresis after subcutaneous administration of G-CSF. Rapid engraftment occurred since 5.6 x 10(9)/l leukocytes were achieved on day +9 post-transplant. At this time a severe immune haemolytic syndrome occurred and direct antiglobulin test was positive (IgG and C3d). Elution showed an anti-A specificity. Evolution was rapidly unfavourable related to multiorgan failure. The patient died on day +20 post-transplant.

    背景与目标: 一名38岁的男性,血型A,是从他完全匹配的姐姐的血型O中异位移植的,用于多发性骨髓瘤。供体的抗A抗体IgG和IgM滴度很低。皮下给药G-CSF后,通过白细胞分离术收集异体外周血干细胞。由于移植后第9天获得了5.6 x 10(9)/ l白细胞,因此发生了快速植入。这时发生了严重的免疫溶血综合症,直接抗球蛋白测试为阳性(IgG和C3d)。洗脱显示出抗A特异性。与多器官衰竭有关的进化迅速不利。该患者在移植后的第20天死亡。

  • 【无细胞翻译过程中的异寡聚去唾液酸糖蛋白受体复合物的组装。】 复制标题 收藏 收藏
    DOI:10.1073/pnas.87.12.4854 复制DOI
    作者列表:Sawyer JT,Doyle D
    BACKGROUND & AIMS: :We have translated RNAs for the two rat asialoglycoprotein receptor polypeptides together in a cell-free system containing dog pancreatic microsomes and immunoprecipitated the products with antibodies that distinguish the two proteins. In this system the proteins oligomerize, as judged by their coprecipitation with either of the subunit-specific antisera. Oligomerization does not occur between subunits synthesized without microsomes or between subunits synthesized on separate microsomes mixed during detergent solubilization. Thus, oligomerization occurs within the microsomal membrane. We calculate that oligomerization proceeds with an efficiency of approximately 85%. The receptor complex appears to represent a specific oligomer because it excludes a third membrane glycoprotein synthesized in the same reaction. Oligomerization of the asialoglycoprotein receptor in vitro should provide a useful system to study the assembly of a membrane-protein complex.
    背景与目标: :我们已经在包含狗胰微粒体的无细胞系统中一起翻译了两种大鼠去唾液酸糖蛋白受体多肽的RNA,并使用区分这两种蛋白的抗体对产品进行了免疫沉淀。在该系统中,蛋白质通过与任何亚基特异性抗血清共沉淀来寡聚。在没有微粒体的情况下合成的亚基之间或在去污剂溶解过程中混合的单独微粒体上合成的亚基之间不会发生低聚。因此,低聚发生在微粒体膜内。我们计算出低聚进行的效率约为85%。受体复合物似乎代表特定的寡聚物,因为它排除了在同一反应中合成的第三膜糖蛋白。脱唾液酸糖蛋白受体的体外低聚应该提供一个有用的系统来研究膜-蛋白复合物的组装。
  • 【重组人可溶性肿瘤坏死因子受体融合蛋白作为同种异体造血干细胞移植后类固醇难治性移植物抗宿主病的治疗方法。】 复制标题 收藏 收藏
    DOI:10.1002/ajh.20752 复制DOI
    作者列表:Busca A,Locatelli F,Marmont F,Ceretto C,Falda M
    BACKGROUND & AIMS: :Etanercept is a recombinant human soluble tumor necrosis factor (TNF-alpha) receptor fusion protein that inhibits TNF-alpha, a major mediator in the pathogenesis of graft-versus-host disease (GVHD). The purpose of our study was to evaluate the safety and efficacy of etanercept therapy in 21 patients with steroid-refractory acute GVHD (aGVHD) (n = 13) and chronic GVHD (cGVHD) (n = 8). Etanercept 25 mg was given subcutaneously twice weekly for 4 weeks followed by 25 mg weekly for 4 weeks. At the time of initiation of etanercept, 14 patients had skin, 13 had gastro-intestinal, 5 had liver, 5 had pulmonary, and 4 had oral involvement. Twelve patients (57%) completed 12 doses of therapy. Overall, 11 of 21 patients (52%) responded to the treatment with etanercept, including 6 patients (46%) with aGVHD [n = 4 complete response (CR), n = 2 partial response (PR)] and 5 patients (62%) with cGVHD (n = 1 CR, n = 4 PR). Clinical responses were most commonly seen in patients with refractory gut aGVHD with 55% of the patients having a CR and 9% having a PR. CMV reactivation occurred in 48% of patients, bacterial infections in 14% of patients, and fungal infections in 19% of patients. Fourteen patients (67%) were alive after a median follow-up of 429 days (range 71-1007 days) since initiation of etanercept. Seven patients died, 3 of infections, 2 of refractory aGVHD, and 2 of disease progression. In conclusion, our preliminary data indicate that etanercept is well tolerated and can induce a high response rate in patients with steroid-refractory aGVHD and cGVHD, particularly in the setting of GI involvement.
    背景与目标: :Etanercept是一种重组人类可溶性肿瘤坏死因子(TNF-alpha)受体融合蛋白,可抑制TNF-alpha(一种在移植物抗宿主病(GVHD)发病机理中的主要介体)。本研究的目的是评估依那西普治疗21例激素抵抗性急性GVHD(aGVHD)(n = 13)和慢性GVHD(cGVHD)(n = 8)患者的安全性和有效性。每周两次皮下给予Etanercept 25 mg,持续4周,然后每周25 mg,持续4周。依那西普开始治疗时,有14例皮肤,13例胃肠,5例肝,5例肺,4例经口受累。 12名患者(57%)完成了12剂治疗。总体上,在21名患者中有11名患者(52%)对依那西普治疗有反应,包括6名患者(46%)患有aGVHD [n = 4完全缓解(CR),n = 2部分缓解(PR)]和5例(62 %)和cGVHD(n = 1 CR,n = 4 PR)。临床反应最常见于顽固性肠aGVHD患者,其中55%的患者为CR,9%的患者为PR。 CMV重新激活发生在48%的患者中,细菌感染发生在14%的患者中,而真菌感染发生在19%的患者中。自依那西普开始接受中位随访429天(71-1007天)后,有14名患者(67%)还活着。 7例患者死亡,3例感染,2例难治性aGVHD死亡,2例疾病进展。总之,我们的初步数据表明,依那西普耐受性好,在类固醇难治性aGVHD和cGVHD患者中可引起较高的应答率,尤其是在胃肠道受累的情况下。
  • 【T-T细胞相互作用是由粘附分子介导的。】 复制标题 收藏 收藏
    DOI:10.1002/eji.1830201015 复制DOI
    作者列表:Brod SA,Purvee M,Benjamin D,Hafler DA
    BACKGROUND & AIMS: :The mechanism by which T cells signal other T cells is not well defined. This was investigated by studying the ability of circulating T cells to induce the proliferation of autologous T cell clones. Peripheral blood T cells activated by cross-linking of the CD3/T cell receptor complex, which increased the expression of cell adhesion molecules LFA-1, LFA-3 and ICAM-1, induced the proliferation of autologous T cell clones. Irradiated antigen-activated peripheral blood T cells could also induce the proliferation of T cell clones which could not recognize that antigen. T-T cell activation required cell contact, was not major histocompatibility complex (MHC) restricted and was blocked by monoclonal antibodies directed against adhesion molecules CD2 and LFA-3 but was not blocked by antibody to class II MHC determinants. As CD2 is the natural ligand for LFA-3, increased expression of T cell surface adhesion molecules LFA-1, ICAM-1 and particularly LFA-3 during an inflammatory response may rapidly recruit T cells that are activated through the CD2 pathway. These results allow a simplified model to explain how relatively few antigen/MHC-specific T cells can recruit large numbers of non-antigen-specific T cells in the generation of an inflammatory response and postulates a novel role of the CD2 molecule in T cell immune function.
    背景与目标: :T细胞向其他T细胞发出信号的机制尚不明确。通过研究循环T细胞诱导自体T细胞克隆增殖的能力,对此进行了研究。通过CD3 / T细胞受体复合物交联而活化的外周血T细胞增加了细胞粘附分子LFA-1,LFA-3和ICAM-1的表达,诱导了自体T细胞克隆的增殖。辐射的抗原活化的外周血T细胞也可以诱导不能识别该抗原的T细胞克隆的增殖。 T-T细胞活化需要细胞接触,不受主要组织相容性复合物(MHC)的限制,并且被针对粘附分子CD2和LFA-3的单克隆抗体所阻断,但未被II类MHC决定簇的抗体所阻断。由于CD2是LFA-3的天然配体,因此在炎症反应期间T细胞表面粘附分子LFA-1,ICAM-1尤其是LFA-3的表达增加,可能会迅速募集通过CD2途径激活的T细胞。这些结果使简化的模型可以解释相对较少的抗原/ MHC特异性T细胞在炎症反应的产生中如何募集大量非抗原特异性T细胞,并推测CD2分子在T细胞免疫中的新作用功能。
  • 【抗原特异性T细胞克隆在胶原疾病中的意义:用新型T细胞克隆性评估系统进行分析。】 复制标题 收藏 收藏
    DOI:10.2169/internalmedicine.36.242 复制DOI
    作者列表:Yamamoto K
    BACKGROUND & AIMS: The involvement of antigen-specific T cells in the pathogenesis of collagen diseases is still controversial. The final stages of collagen diseases are usually characterized by the dominance of inflammation. Therefore, antigen non-specific factors, such as inflammatory cytokines, probably play an important role in this process. On the other hand, the methods available to analyze the antigen-specific aspects of the immune response are still limited. Here we review our novel system of T cell clonality analysis based on the idea that activated antigen-specific T cells should form accumulating clones among the lymphocyte population. Using this method, dynamic changes of clonal accumulation of T cells could be evaluated during antigenic stimulation in vivo and in vitro. The significance of antigen-specific T cell clones in collagen diseases is discussed using data obtained from patients with rheumatoid arthritis and systemic lupus erythematosus.

    背景与目标: 抗原特异性T细胞是否参与胶原蛋白疾病的发病机制仍存在争议。胶原蛋白疾病的最后阶段通常以炎症占优势为特征。因此,抗原非特异性因子,例如炎性细胞因子,可能在此过程中起重要作用。另一方面,可用于分析免疫应答的抗原特异性方面的方法仍然有限。在这里,我们基于激活的抗原特异性T细胞应在淋巴细胞群体中形成累积克隆的想法,回顾了我们的T细胞克隆性分析的新系统。使用这种方法,可以在体内和体外抗原刺激过程中评估T细胞克隆积累的动态变化。利用类风湿性关节炎和系统性红斑狼疮患者获得的数据,讨论了抗原特异性T细胞克隆在胶原蛋白疾病中的重要性。

  • 【电离辐射以肺内不同的组织学模式介导细胞粘附分子的表达。】 复制标题 收藏 收藏
    DOI: 复制DOI
    作者列表:Hallahan DE,Virudachalam S
    BACKGROUND & AIMS: Inflammatory cell infiltration of the lung is a predominant histopathological change that occurs during radiation pneumonitis. Emigration of inflammatory cells from the circulation requires the interaction between cell adhesion molecules on the vascular endothelium and molecules on the surface of leukocytes. We studied the immunohistochemical pattern of expression of cell adhesion molecules in lungs from mice treated with thoracic irradiation. After X-irradiation, the endothelial leukocyte adhesion molecule 1 (ELAM-1; E-selectin) was primarily expressed in the pulmonary endothelium of larger vessels and minimally in the microvascular endothelium. Conversely, the intercellular adhesion molecule 1 (ICAM-1; CD54) was expressed in the pulmonary capillary endothelium and minimally in the endothelium of larger vessels. Radiation-mediated E-selectin expression was first observed at 6 h, whereas ICAM-1 expression initially increased at 24 h after irradiation. ICAM-1 and E-selectin expression persisted for several days. P-selectin is constitutively expressed in Weibel-Palade bodies in the endothelium, which moved to the vascular lumen within 30 min after irradiation. P-selectin was not detected in the pulmonary endothelium at 6 h after irradiation. The radiation dose required for increased cell adhesion molecule expression within the pulmonary vascular endothelium was 2 Gy, and expression increased in a dose-dependent manner. These data demonstrate that ICAM-1 and E-selectin expression is increased in the pulmonary endothelium following thoracic irradiation. The pattern of expression of E-selectin, P-selectin, and ICAM-1 is distinct from one another.

    背景与目标: 肺炎性细胞浸润是放射性肺炎期间发生的主要组织病理学变化。炎性细胞从循环系统的迁移需要血管内皮细胞粘附分子与白细胞表面分子之间的相互作用。我们研究了用胸腔照射治疗的小鼠肺中细胞粘附分子表达的免疫组织化学模式。 X射线照射后,内皮白细胞粘附分子1(ELAM-1; E-选择素)主要在较大血管的肺内皮中表达,而在微血管内皮中则最低表达。相反,细胞间粘附分子1(ICAM-1; CD54)在肺毛细血管内皮中表达,而在较大血管的内皮中表达最少。辐射介导的E-选择素表达首先在6 h观察到,而ICAM-1表达最初在辐射后24 h增加。 ICAM-1和E-选择素表达持续数天。 P-选择蛋白在内皮的Weibel-Palade体中组成性表达,在照射后30分钟内移至血管腔。照射后6 h在肺内皮中未检测到P-选择素。肺血管内皮细胞中细胞粘附分子表达增加所需的辐射剂量为2 Gy,并且表达以剂量依赖性方式增加。这些数据表明,胸腔照射后,肺内皮中的ICAM-1和E-选择蛋白表达增加。 E-选择素,P-选择素和ICAM-1的表达模式彼此不同。

  • 【MHC I类区域对巨细胞动脉炎遗传易感性的贡献。】 复制标题 收藏 收藏
    DOI:10.1093/rheumatology/kel324 复制DOI
    作者列表:Gonzalez-Gay MA,Rueda B,Vilchez JR,Lopez-Nevot MA,Robledo G,Ruiz MP,Fernández O,Garcia-Porrua C,Gonzalez-Escribano MF,Martín J
    BACKGROUND & AIMS: OBJECTIVE:The aim of this study was to assess the potential contribution of HLA-class I MICA and HLA-B gene polymorphisms towards the pathogenesis of giant cell arteritis (GCA). METHODS:Ninety-eight biopsy-proven GCA patients and 225 ethnically matched controls from Lugo, Northwest Spain, were genotyped for the MICA-TM microsatellite polymorphism using a polymerase chain reaction (PCR)-based method. Genotyping of HLA-B was performed using PCR and detection with a reverse sequence-specific oligonucleotide (SSO) probes system. RESULTS:A significant difference in the distribution of the alleles of MICA between patient and control groups (P = 0.005) was found. This was due to an increased frequency of the MICA A5 allele in GCA patients compared with controls (26 vs 13.6%; P = 0.0001; P(C) = 0.0005; OR 2.2, 95% CI 1.4-3.4). In addition, the HLA-B*15 allele showed a higher frequency in GCA patients compared with controls (P = 0.004; P(C) = 0.04; OR 2.7, 95% CI 1.3-5.7). Interestingly, the association observed with the MICA A5 allele seems to be independent of linkage disequilibrium with HLA-B, as well as independent of that previously described with HLA-DRB1*04. Remarkably, simultaneous presence of MICA A5 and HLA-B*15 or HLA-DRB1*04 genetic markers leads to an increase in the OR obtained for each individual genetic marker (MICA A5 + B*15 OR 3.2; MICA A5 + DRB1*04 OR 5.8). CONCLUSIONS:Our results provide the first evidence that the MICA and HLA-B genes are independently associated with the genetic susceptibility to GCA, and suggest that several genes within the MHC might have independent effects in the susceptibility to this systemic vasculitis.
    背景与目标: 目的:本研究旨在评估HLA I类MICA和HLA-B基因多态性对巨细胞性动脉炎(GCA)发病的潜在作用。
    方法:采用聚合酶链反应(PCR)方法,对来自西班牙西北部卢戈市的98例活检证实的GCA患者和225名种族匹配的对照进行了MICA-TM微卫星多态性的基因分型。使用PCR进行HLA-B的基因分型,并使用反向序列特异性寡核苷酸(SSO)探针系统进行检测。
    结果:在患者和对照组之间,MICA等位基因的分布存在显着差异(P = 0.005)。这是由于与对照相比,GCA患者中MICA A5等位基因的频率增加(26比13.6%; P = 0.0001; P(C)= 0.0005; OR 2.2,95%CI 1.4-3.4)。此外,与对照相比,GCA患者的HLA-B * 15等位基因频率更高(P = 0.004; P(C)= 0.04; OR 2.7,95%CI 1.3-5.7)。有趣的是,与MICA A5等位基因所观察到的关联似乎独立于与HLA-B的连锁不平衡,也独立于先前对HLA-DRB1 * 04的描述。值得注意的是,同时存在MICA A5和HLA-B * 15或HLA-DRB1 * 04遗传标记会导致每个单独的遗传标记获得的OR升高(MICA A5 B * 15或3.2; MICA A5 DRB1 * 04 OR 5.8 )。
    结论:我们的结果提供了第一个证据,表明MICA和HLA-B基因与对GCA的遗传易感性独立相关,并表明MHC中的几个基因可能对该系统性血管炎的易感性具有独立影响。
  • 【通过过继转移CD4抗肿瘤T细胞杀死原位大鼠腺癌13762需要细胞表面MHC II类分子的肿瘤表达。】 复制标题 收藏 收藏
    DOI:10.1006/cimm.1997.1122 复制DOI
    作者列表:Frey AB,Cestari S
    BACKGROUND & AIMS: CD4+ anti-tumor T cells reactive with rat adenocarcinoma 13762 kill tumor in vitro and cause regression of tumor in vivo. The role of various host immune cells in CD4+ T-cell-mediated tumor elimination in vivo was investigated by adoptive transfer of anti-tumor T cell clones to recipients that were selectively depleted of individual immune cell types. By these means, macrophages and NK cells were found to be required for tumor killing. Depletion of host CD4+ T cells, CD8+ T cells, or neutrophils was without effect on tumor elimination by anti-tumor T cells. An essential role for antigen receptor-negative NK cells is likely dependent upon secretion of IFN-gamma from NK cells since treatment of tumor recipients with anti-IFN-gamma antibody prior to adoptive transfer and tumor challenge abrogated T cell killing, resulting in progressive tumor growth. Viability of adenocarcinoma 13762 or anti-tumor T cells was unaffected by treatment with either IFN-gamma or anti-IFN-gamma antibody in vitro, but cell surface MHC class II expression was induced in tumor cells by exposure to IFN-gamma. In addition, tumor cells were isolated from tumor-bearing animals by absorption using anti-MHC class II antibody, demonstrating that 13762 tumor expresses cell surface MHC class II antigens in situ. However, if hosts were depleted of NK cells before tumor challenge, MHC class II+ tumor was not recovered. Collectively these results suggest that adenocarcinoma 13762 is eliminated by MHC class II-restricted CD4+ T cells by direct tumor killing.

    背景与目标: 与大鼠腺癌13762反应的CD4抗肿瘤T细胞在体外杀死肿瘤并在体内引起肿瘤消退。通过将抗肿瘤T细胞克隆过继转移到选择性清除了个体免疫细胞类型的受体上,研究了各种宿主免疫细胞在体内CD4 T细胞介导的肿瘤消除中的作用。通过这些手段,发现杀死肿瘤需要巨噬细胞和NK细胞。宿主CD4 T细胞,CD8 T细胞或嗜中性白细胞的耗竭对抗肿瘤T细胞对肿瘤的消除没有影响。抗原受体阴性NK细胞的重要作用可能取决于NK细胞分泌IFN-γ,因为在过继转移和肿瘤攻击之前用抗IFN-γ抗体治疗肿瘤受体可以消除T细胞杀伤,从而导致进行性肿瘤生长。体外用IFN-γ或抗IFN-γ抗体治疗不会影响腺癌13762或抗肿瘤T细胞的存活率,但通过暴露于IFN-γ诱导了肿瘤细胞的细胞表面MHC II类表达。另外,通过使用抗MHC II类抗体的吸收从荷瘤动物中分离出肿瘤细胞,表明13762肿瘤原位表达细胞表面MHC II类抗原。但是,如果宿主在肿瘤攻击前已耗尽NK细胞,则无法恢复MHC II类肿瘤。这些结果共同表明,通过直接杀死肿瘤,MHC II类限制性CD4 T细胞可消除13762腺癌。

  • 【垂体激素调节胸腺细胞和胸腺上皮细胞之间的细胞间相互作用。】 复制标题 收藏 收藏
    DOI:10.1016/s0165-5728(97)00031-3 复制DOI
    作者列表:de Mello-Coelho V,Villa-Verde DM,Dardenne M,Savino W
    BACKGROUND & AIMS: The thymic microenvironment plays a key role in the intrathymic T-cell differentiation. It is composed of a tridimensional network of epithelial cells whose physiology is controlled by extrinsic circuits such as neuroendocrine axes. Herein we show that the expression of extracellular matrix ligands and receptor by cultured thymic epithelial cells is upregulated by prolactin (PRL) and growth hormone (GH), the latter apparently occurring via insulin-like growth factor I (IGF-I). Thymocyte release from the lymphoepithelial complexes, thymic nurse cells, as well as the reconstitution of these complexes are enhanced by PRL, GH or IGF-I. Treatment of a mouse thymic epithelial cell line with these hormones induced an increase in thymocyte adhesion, an effect significantly prevented in the presence of antibodies to fibronectin, laminin or respective receptors VLA-5 and VLA-6. Our data suggest that the in vitro changes in thymocyte/thymic epithelial cell interactions induced by pituitary hormones are partially mediated by the enhancement of extracellular matrix ligands and receptors.

    背景与目标: 胸腺微环境在胸腺内T细胞分化中起关键作用。它由上皮细胞的三维网络组成,其上皮细胞的生理受到外在回路(如神经内分泌轴)的控制。本文中我们显示,培养的胸腺上皮细胞的细胞外基质配体和受体的表达被催乳素(PRL)和生长激素(GH)上调,后者显然是通过胰岛素样生长因子I(IGF-1)发生的。 PRL,GH或IGF-I增强了从淋巴上皮复合物,胸腺护士细胞释放胸腺细胞以及这些复合物的重构。用这些激素处理小鼠胸腺上皮细胞系可诱导胸腺细胞粘附增加,在存在针对纤连蛋白,层粘连蛋白或相应受体VLA-5和VLA-6的抗体的情况下,该作用被显着阻止。我们的数据表明,垂体激素诱导的胸腺细胞/胸腺上皮细胞相互作用的体外变化部分由细胞外基质配体和受体的增强介导。

  • 【缺氧条件下的肿瘤基质细胞相互作用通过肝细胞生长因子/ c-Met途径增加了胰腺癌细胞的侵袭性。】 复制标题 收藏 收藏
    DOI:10.1002/ijc.22178 复制DOI
    作者列表:Ide T,Kitajima Y,Miyoshi A,Ohtsuka T,Mitsuno M,Ohtaka K,Koga Y,Miyazaki K
    BACKGROUND & AIMS: :The hypoxic environment in tumor is reported to play an important role in pancreatic cancer progression. The interaction between stromal and cancer cells also contributes to the malignant behavior of pancreatic cancer. In the present study, we investigated whether hypoxic stimulation affects stromal as well as pancreatic cancer cells. Our findings demonstrated that hypoxia remarkably elevated the HIF-1alpha expression in both pancreatic cancer (PK8) and fibroblast cells (MRC5). Hypoxic stimulation accelerated the invasive activity of PK8 cells, and invasiveness was thus further accelerated when the hypoxic PK8 cells were cultured with conditioned medium prepared from hypoxic MRC5 cells (hypoxic conditioned medium). MMP-2, MMP-7, MT1-MMP and c-Met expressions were increased in PK8 cells under hypoxia. Hypoxic stimulation also increased the hepatocyte growth factor (HGF) secretion from MRC5 cells, which led to an elevation of c-Met phosphorylation in PK8 cells. Conversely, the elevated cancer invasion, MMP activity and c-Met phosphorylation of PK8 cells were reduced by the removal of HGF from hypoxic conditioned medium. In immunohistochemical study, the HIF-1alpha expression was observed in surrounding stromal as well as pancreatic cancer cells, thus indicating hypoxia exists in both of cancer and stromal cells. Moreover, the stromal HGF expression was found to significantly correlate with not only the stromal HIF-1alpha expression but also the c-Met expression in cancer cells. These results indicate that the hypoxic environment within stromal as well as cancer cells activates the HGF/c-Met system, thereby contributing to the aggressive invasive features of pancreatic cancer.
    背景与目标: :据报道肿瘤中的低氧环境在胰腺癌的进展中起重要作用。基质细胞与癌细胞之间的相互作用也有助于胰腺癌的恶性行为。在本研究中,我们调查了低氧刺激是否影响基质和胰腺癌细胞。我们的研究结果表明,缺氧显着提高了胰腺癌(PK8)和成纤维细胞(MRC5)中HIF-1alpha的表达。低氧刺激加速了PK8细胞的侵袭活性,因此,当用由低氧MRC5细胞制备的条件培养基(低氧条件培养基)培养低氧PK8细胞时,侵袭性进一步加快。在缺氧条件下,PK8细胞中的MMP-2,MMP-7,MT1-MMP和c-Met表达增加。缺氧刺激还增加了MRC5细胞的肝细胞生长因子(HGF)分泌,这导致PK8细胞中c-Met磷酸化的升高。相反,通过从低氧条件培养基中除去HGF,可以降低PK8细胞的癌浸润,MMP活性和c-Met磷酸化升高。在免疫组织化学研究中,在周围的基质细胞和胰腺癌细胞中均观察到了HIF-1alpha的表达,因此表明在癌细胞和基质细胞中均存在缺氧。此外,发现基质HGF表达不仅与癌细胞中的基质HIF-1α表达而且与c-Met表达显着相关。这些结果表明基质以及癌细胞内的低氧环境激活了HGF / c-Met系统,从而促进了胰腺癌的侵袭性侵袭性特征。
  • 15 B-cell memory: are subsets necessary? 复制标题 收藏 收藏

    【B细胞记忆:是否需要子集?】 复制标题 收藏 收藏
    DOI:10.1038/nri1938 复制DOI
    作者列表:Tarlinton D
    BACKGROUND & AIMS: :B-cell memory is provided by populations of quiescent memory B cells and long-lived plasma cells. Whereas it is clear that both of these cell populations arise from germinal centres, the signals and circumstances that trigger germinal-centre B cells to enter and then persist in memory compartments are poorly defined. Here, I propose that germinal centres produce memory B cells and plasma cells throughout the immune response and that memory B cells arise by the emigration of B cells that are chosen at random from the pool available in the germinal centre. The ability of such emigrants to survive as memory B cells depends on their germinal-centre 'history', with the persistence of high-affinity B-cell variants being favoured.
    背景与目标: :B细胞记忆由静态记忆B细胞和长寿浆细胞群体提供。显然,这两个细胞群均起源于生发中心,但触发生发中心B细胞进入并随后在记忆区室中存留的信号和环境的定义不明确。在这里,我建议生发中心在整个免疫反应过程中都会产生记忆B细胞和浆细胞,而记忆B细胞则是通过迁移B细胞而产生的,这些B细胞是从生发中心可用的池中随机选择的。这些移出者作为记忆B细胞存活的能力取决于它们的生发中心“历史”,而高亲和力B细胞变体的持久性受到青睐。

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