The vascular endothelial growth factor receptor Flt-1 mediates biological activities - Implications for a functional role of placenta growth factor in monocyte activation and chemotaxis
The vascular endothelial growth factor receptor Flt-1 mediates biological activities - Implications for a functional role of placenta growth factor in monocyte activation and chemotaxis
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DOI：
10.1074/jbc.271.30.17629
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发表时间：
1996-07-26
影响因子：
4.8
通讯作者：
Risau, W
中科院分区：
文献类型：
--
作者：
Clauss, M;Weich, H;Risau, W
血管内皮生长因子（VEGF）的两种不同受体，酪氨酸激酶受体Flt-1和Flk-1/KDR，已被描述。在这项研究中，我们表明，单核细胞，与内皮细胞相反，只表达VEGF受体Flt-1，并且该受体特异性结合VEGF同系物胎盘生长因子（PlGF）。VEGF和PlGF都以相等的剂量刺激单核细胞中的组织因子产生和趋化性。相反，表达Flt-1和Flk-1/KDR受体的内皮细胞在用VEGF刺激后比用PlGF刺激后产生更多的组织因子。抗KDR受体的中和抗体将内皮细胞中VEGF刺激的组织因子诱导降低至仅用PlGF刺激获得的水平，但不影响内皮细胞中PlGF诱导的组织因子诱导，也不影响单核细胞中VEGF依赖性组织因子的产生，这些研究结果强烈表明，Flt-1作为单核细胞和内皮细胞中VEGF和PlGF的功能性受体，并鉴定该受体作为单核细胞募集和促凝血活性的介体。
Two distinct receptors for vascular endothelial growth factor (VEGF), the tyrosine kinase receptors Flt-1 and Flk-1/KDR, have been described, In this study we show that monocytes, in contrast to endothelium, express only the VEGF receptor Flt-1, and that this receptor specifically binds also the VEGF homolog placenta growth factor (PlGF). Both VEGF and PlGF stimulate tissue factor production and chemotaxis in monocytes at equivalent doses. In contrast, endothelial cells expressing both the Flt-1 and the Flk-1/KDR receptors produce more tissue factor upon stimulation with VEGF than after stimulation with PlGF. Neutralizing antibodies to the KDR receptor reduce the VEGF-stimulated tissue factor induction in endothelial cells to levels obtained by stimulation with PlGF alone, but do not affect PlGF-induced tissue factor induction in endothelial cells nor the VEGF dependent tissue factor production in monocytes, These findings strongly suggest Flt-1 as a functional receptor for VEGF and PlGF in monocytes and endothelial cells and identify this receptor as a mediator of monocyte recruitment and procoagulant activity.