Migration of human monocytes in response to vascular endothelial growth factor (VEGF) is mediated via the VEGF receptor flt-1
Migration of human monocytes in response to vascular endothelial growth factor (VEGF) is mediated via the VEGF receptor flt-1
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DOI：
10.1182/blood.v87.8.3336.bloodjournal8783336
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发表时间：
1996-04-15
期刊：
影响因子：
20.3
通讯作者：
Marme, D
中科院分区：
文献类型：
--
作者：
Barleon, B;Sozzani, S;Marme, D
据报道，用从肿瘤细胞上清液中分离的血管内皮生长因子（VEGF）处理人单核细胞可诱导单核细胞活化和迁移。在这项研究中，我们发现重组人VEGF（165）和VEGF（121）在65至250 pmol/L时对人单核细胞迁移的影响最大。VEGF（165）的趋化活性被VEGF的特异性抗血清、VEGF（165）的热处理和蛋白激酶抑制剂抑制。此外，我们可以证明VEGF刺激的单核细胞迁移是由百日咳毒素敏感的GTP结合蛋白介导的。胎盘生长因子（PlGF（152））是一种与VEGF相关的肝素结合生长因子，在2.5 - 25 pmol/L浓度下也对单核细胞具有趋化性。根据这些发现，人单核细胞显示与I-125-VEGF的特异性和饱和结合（165）（1 - 1.5 nmol/L的半数最大结合）。使用北方印迹分析，我们可以进一步显示人单核细胞仅表达VEGF受体类型fit-1的基因，但不表达第二种已知VEGF受体KDR的基因。静息单核细胞仅表达低水平的fit-1基因。人单核细胞短暂暴露于脂多糖（一种原型单核细胞激活剂）（2至4小时）导致fit-1 mRNA水平显著上调。这里呈现的结果表明，响应于VEGF和最可能响应于PIGF（152）的单核细胞趋化性由fit-1介导，因此显示VEGF受体fit-1的可能功能。(C)1996年，美国血液学会。
Treatment of human monocytes with vascular endothelial growth factor (VEGF) isolated from tumor cell supernatants was reported to induce monocyte activation and migration. In this study we show that recombinant human VEGF(165) and VEGF(121) had a maximal effect on human monocyte migration at 65 to 250 pmol/L. Chemotactic activity of VEGF(165) was inhibited by a specific antiserum against VEGF, by heat treatment of VEGF(165), and by protein kinase inhibitors. In addition, we could show that VEGF-stimulated monocyte migration is mediated by a pertussis toxin-sensitive GTP-binding protein. Placenta growth factor (PIGF(152)), a heparin-binding growth factor related to VEGF, was also chemotactic for monocytes at concentrations between 2.5 and 25 pmol/L. In accordance with these findings, human monocytes showed specific and saturable binding for I-125-VEGF(165) (half-maximal binding at 1 to 1.5 nmol/L). Using Northern blot analysis, we further could show that human monocytes express only the gene for the VEGF receptor type, fit-1, but not for the second known VEGF receptor, KDR. Resting monocytes expressed low levels of fit-1 gene only. Brief exposure (2 to 4 hours) of human monocytes to lipopolysaccharids, a prototypic monocyte activator, led to a significant upregulation of the fit-1 mRNA level. The results presented here suggest that monocyte chemotaxis in response to VEGF and most likely to PIGF(152) is mediated by fit-1 and thus show a possible function for the VEGF-receptor fit-1. (C) 1996 by The American Society of Hematology.