Department of Physiology, University of Siena, Via Aldo Moro, 53100 Siena, Italy.
J Leukoc Biol. 2010 Mar;87(3):365-9. doi: 10.1189/jlb.0709460. Epub 2009 Nov 4.
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 p66Shc-/- mouse splenocytes. Accordingly, the angiogenic response induced by the supernatants from hypoxic p66Shc-/- 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.
免疫细胞在血管生成的发生中起着重要作用。在这里，我们报告称，VEGF 是缺氧条件下 T 细胞表达的主要促血管生成因子，缺氧是炎症和肿瘤微环境的共同特征。缺氧 T 细胞的上清液在鸡胚 CAM 上具有高度的血管生成活性。用中和抗 VEGF 抗体可以阻断血管生成反应，而 rVEGF 则可以模拟这种反应。有趣的是，在过表达衔接蛋白 p66Shc 的 Jurkat T 细胞中，缺氧诱导的 VEGF 表达上调，但不表达无活性的 S36 p66Shc 突变体，而 p66Shc-/- 小鼠脾细胞中则没有这种上调。因此，与野生型对照相比，来自缺氧 p66Shc-/- 脾细胞的上清液诱导的血管生成反应显著降低。总之，缺氧 T 细胞可能通过一种新的 VEGF 介导的机制促进血管生成，其中 p66Shc 作为一个正调节剂发挥作用。
