氧化低密度脂蛋白功能性调节人内皮细胞的生长调节致癌基因α

目的　探讨oxLDL对人内皮细胞的CXC亚家族趋化因子GROα的调节作用及生理意义。方法　超高速离心得LDL ,氧化后得oxLDL。逆转录PCR分析人内皮细胞系ECV30 4细胞GROαmRNA。GAPDH被用作PCR中正常改变的对照物。酶联免疫检测仪测定ECV30 4细胞表面连接及分泌到溶液中的GROα蛋白。静态细胞粘附试验测定ECV30 4细胞表面连接的GROα蛋白的生理意义。结果　正常ECV30 4细胞不表达GROαmRNA ;OxLDL显著调节其表达 ,诱导效应首先出现在处理后 1h ,最大在 2h ,在 4h时下降。相比较 ,LDL对其mRNA表达没有影响。正常ECV30 4细胞低水平表达细胞表面的GROα蛋白。OxLDL呈浓度依赖性、时间依赖性地上调其表面的GROα蛋白。相比较 ,LDL对其表面表达的GROα蛋白无调节作用。OxLDL对ECV30 4细胞分泌到细胞溶液中GROα蛋白很少有影响。 4 0 μg/mloxLDL处理ECV30 4细胞 2 4h ,造成显著的人单核细胞系U937细胞粘附到ECV30 4细胞数目的增加。用GROα抗体预处理oxLDL刺激的ECV30 4细胞 ,可显著减低U937细胞粘附到ECV30 4细胞的U937细胞数目 (大约 2 / 3)。结论　oxLDL可能功能性上调内皮细胞GROα的表达。     

Human monocyte-derived dendritic cells expressing both chemotactic cytokines IL-8, MCP-1, RANTES and their receptors, and their selective migration to these chemokines

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趋化性细胞因子与乳腺癌的转移

远处转移是乳腺癌致死和预后较差的重要原因，而在乳腺癌转移中，趋化性细胞因子扮演着重要角色，乳腺癌细胞高表达某些趋化性细胞因子及某些受体，通过趋化性细胞因子与其受体的相互作用，趋化吞噬细胞及淋巴细胞浸润，促使癌细胞侵入正常组织及血管生成，形成转移肿瘤。本文主要综述了近年研究较多的趋化性细胞因子受体CXCR4及趋化性细胞因子RANTES、IL-8、MCP-1等在乳腺癌转移中的作用。     

趋化因子及其在肿瘤免疫治疗中的应用

趋化因子是一类调节白细胞迁移的超家族。其在肿瘤的生物学行为中表现出双向的调节作用。部分趋化因子通过趋化和调节免疫效应细胞的功能来发挥抗肿瘤免疫作用。全文综述了趋化因子及其受体的结构与功能,并阐述了其在肿瘤免疫治疗中的应用。     

反义肽核酸抑制树突细胞趋化因子受体CCR7表达的实验研究

目的探讨靶向趋化因子受体CCR7的反义肽核酸(PNA)对树突细胞(DCs)CCR7的表达及趋化活性的影响。方法体外培养大鼠骨髓来源DCs,设计靶向CCR7mRNA翻译起始区的反义PNA,以随机PNA、空白组为对照处理体外培养7d的DCs,分别于24h,48h,72h后收集细胞,利用Western-blot和逆转录聚合酶链反应(RT-PCR)检测反义PNA对CCR7分子表达的影响,通过趋化实验检测DCs的趋化活性。结果DCs经PNA处理后24h,各组DCs其CCR7表达无明显差别,在48h,Western-blot检测显示反义PNA组CCR7蛋白表达明显低于对照组,而RT-PCR检测在mRNA水平却无明显差别。在72h,反义PNA组CCR7的表达在不同水平均明显低于对照组。经趋化实验证实,在48h以后反义PNA组DCs趋化活性受到明显抑制(P<0.05)。结论CCR7反义PNA能够有效抑制体外培养的大鼠树突细胞趋化因子受体CCR7的表达及其趋化活性,为进一步研究体内应用反义PNA抑制DCs的定向迁移和抗原递呈,调节免疫反应和诱导免疫耐受提供了新的策略。     

非小细胞肺癌间质炎性细胞TAMs、MCs与趋化因子IL-8、MCP-1、MIP-1的相互影响

目的测定非小细胞肺癌MVC和间质中TAMs、MCs计数以及趋化因子IL-8、MCP-1、MIP-1 mRNA的表达，探讨其间相互关系。方法用免疫组化ABC法测定40例非小细胞肺癌组织石蜡切片标本中MV和TAMs、MCs计数。以原位杂交法检测上述标本中IL-8、MCP-1、MIP-1 mRNA的表达情况。分析MV、TAMs、MCs计数和趋化因子阳性表达之间的相互关系。结果40例非小细胞肺癌组织中MV、TAMs、MCs计数和IL-8、MCP-1、MIP-1阳性表达之间以及它们相互之间均存在着密切的正相关。结论非小细胞肺癌间质炎性细胞TAMs、MCs和趋化因子IL-8、MCP-1、MIP-1能够相互协同，共同促进肿瘤血管生成。     

CCR2 and CCR5 chemokine receptors differentially influence the development of autoimmune diabetes in the NOD mouse

The infiltration of monocytes represents an important early event in the development of autoimmune diabetes in NOD mice. Given that chemokines are key regulators of leukocyte trafficking, we examined the requirement for the chemokine receptors β(CC)-chemokine receptor-5 (CCR5) and β(CC)-chemokine receptor-2 (CCR2), which recruit monocytes, in disease development in the NOD mouse. Whereas the onset of diabetes was significantly delayed in CCR2-/-NOD mice (25% at 30 weeks) compared to NOD mice (50% at 28 weeks), the pathogenesis of diabetes was accelerated in CCR5-/-NOD mice (75% at 23 weeks). The rapid development of diabetes in CCR5-/-NOD mice was associated with aggressive destructive insulitis and was accompanied by altered leukocyte migration into islets. In contrast, CCR2-/- NOD mice exhibited delayed inflammatory cell recruitment. Nevertheless, total diabetogenic splenocytes from CCR2-/-NOD and CCR5-/-NOD showed similar capability to adoptively transfer diabetes into NOD.scid recipients. Importantly, our data suggest that targeting of CCR2 may lead to therapies against Type 1 diabetes.     

CCL2 recruits T cells into the brain in a CCR2‐independent manner

CCL2 is a chemokine that can be induced during neuroinflammation to recruit immune cells, but its role in the central nervous system (CNS) is unclear. Our aim was to better understand its role. We induced CCL2 in CNS of naive CCL2‐deficient mice using intrathecally administered replication‐defective adenovirus and examined cell infiltration by flow cytometry. CCL2 expression induced pronounced and unexpected recruitment of regulatory and IFNγ‐producing T cells to CNS from blood, possibly related to defective egress of monocytes from CCL2‐deficient bone marrow. Infiltration also occurred in mice lacking CCR2, a receptor for CCL2. Expression of another receptor for CCL2, CCR4, and CXCR3, a receptor for CXCL10, which was also induced, were both increased in CCL2‐treated CNS. CCR4 was expressed by neurons and astrocytes as well as CD4 T cells, and CXCR3 was expressed by CD4 and CD8 T cells. Chemokine‐recruited T cells did not lead to CNS pathology. Our findings show a role for CCL2 in recruitment of CD4 T cells to the CNS and show that redundancy among chemokine receptors ensures optimal response.