M-CSF induces vascular endothelial growth factor production and angiogenic activity from human monocytes
M-CSF induces vascular endothelial growth factor production and angiogenic activity from human monocytes
复制标题
DOI：
10.4049/jimmunol.171.5.2637
复制
发表时间：
2003-09-01
影响因子：
4.4
通讯作者：
Marsh, CB
中科院分区：
文献类型：
--
作者：
Eubank, TD;Galloway, M;Marsh, CB
人们对免疫反应对恶性肿瘤的影响知之甚少。虽然免疫细胞可以破坏转化细胞，但单核细胞和巨噬细胞在肿瘤部位的靶向和积累可能会促进肿瘤转移。生长因子 M-CSF 对于促进单核细胞存活很重要。由于 M-CSF-/- 小鼠受到保护免受肿瘤转移，我们假设 M-CSF 诱导单核细胞产生促进转移的血管生成因子。在本研究中，我们证明重组人 M-CSF 诱导新鲜分离的正常人单核细胞以剂量依赖性方式产生和释放生长因子血管内皮生长因子 (VEGF)，在培养 5 天时达到峰值。这些单核细胞释放的 VEGF 具有生物活性，因为来自这些 M-CSF 刺激的单核细胞的无细胞上清液诱导 HUVEC 中的管形成。在用来自M-CSF刺激的单核细胞的上清液处理后，这些HUVEC的网络形成被抗VEGF抑制，但不被同基因对照Abs抑制。总的来说，这些数据支持 M-CSF 和单核细胞在 VEGF 产生和血管生成中的重要作用。
The impact of the immune response in malignancy is poorly understood. While immune cells can destroy transformed cells, the targeting and accumulation of monocytes and macrophages at tumor sites may promote tumor metastases. The growth factor M-CSF is important in promoting monocyte survival. Since M-CSF-/- mice are protected against tumor metastases, we hypothesized that M-CSF induced monocytes to produce angiogenic factors that facilitate metastases. In this study we demonstrate that recombinant human M-CSF induces freshly isolated normal human monocytes to produce and release the growth factor vascular endothelial growth factor (VEGF) in a dose-dependent manner, which peaked at 5 days in culture. VEGF released by these monocytes is biologically active, as cell-free supernatants from these M-CSF-stimulated monocytes induced tube formation,in HUVEC. Network formation by these HUVECs after treatment with supernatants from monocytes stimulated with M-CSF were inhibited by anti-VEGF, but not by the isogenic control, Abs. Collectively, these data support an important role for M-CSF and monocytes in VEGF production and angiogenesis.