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首页> 外文期刊>Journal of Leukocyte Biology: An Official Publication of the Reticuloendothelial Society >The adaptor protein p66shc is a positive regulator in the angiogenic response induced by hypoxic T cells
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The adaptor protein p66shc is a positive regulator in the angiogenic response induced by hypoxic T cells

机译:衔接蛋白p66shc在缺氧T细胞诱导的血管生成反应中是一个正调节剂

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Immune cells play an important role in the onset of angiogenesis. Here, we report that VEGF represents the major proangiogenic factor expressed by T cells exposed to hypoxia, a common feature of inflammation and tumor microenvironment. The supernatants of hypoxic T cells were highly angiogenic when delivered on the chick embryo CAM. The angiogenic response was abrogated by a neutralizing anti-VEGF antibody and mimicked by rVEGF. Interestingly, VEGF induction by hypoxia was up-regulated in Jurkat T cells overexpressing the adaptor protein p66Shc but not the inactive S36 p66Shc mutant, and it was abolished in p66Shca?’/a?’ mouse splenocytes. Accordingly, the angiogenic response induced by the supernatants from hypoxic p66Shca?’/a?’ splenocytes was reduced dramatically when compared with the wild-type controls. In conclusion, hypoxic T cells may contribute to the onset of angiogenesis through a novel VEGF-mediated mechanism, where p66Shc acts as a positive regulator.
机译:免疫细胞在血管生成中起重要作用。在这里,我们报道VEGF代表由暴露于缺氧的T细胞表达的主要促血管生成因子,这是炎症和肿瘤微环境的共同特征。低氧T细胞的上清液在鸡胚CAM上递送时具有高度血管生成作用。通过中和性抗VEGF抗体消除了血管生成反应,并通过rVEGF进行了模仿。有趣的是,低氧诱导的VEGF诱导在过表达衔接蛋白p66Shc的Jurkat T细胞中被上调,而在无活性的S36 p66Shc突变体中则没有,并且在p66Shca?/ a?小鼠脾细胞中被废除了。因此,与野生型对照相比,由低氧的p66Shcaα/aβ脾细胞的上清液诱导的血管生成反应显着降低。总之,低氧T细胞可能通过新的VEGF介导的机制促进血管新生,其中p66Shc充当正调节剂。

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