Characterization of vascular permeability factor/vascular endothelial growth factor receptors on mononuclear phagocytes.
Characterization of vascular permeability factor/vascular endothelial growth factor receptors on mononuclear phagocytes.
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DOI：
10.1182/blood.v81.10.2767.bloodjournal81102767
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发表时间：
1993-05
期刊：
影响因子：
20.3
通讯作者：
H. Shen;M. Clauss;J. Ryan;A. Schmidt;P. Tijburg;L. Borden;D. Connolly;D. Stern;J. Kao
中科院分区：
文献类型：
--
作者：
H. Shen;M. Clauss;J. Ryan;A. Schmidt;P. Tijburg;L. Borden;D. Connolly;D. Stern;J. Kao
血管通透性因子/血管内皮生长因子（VPF/VEGF）是一种多肽介质，由某些肿瘤和其他细胞类型精心设计，通过与一类高亲和力结合位点的相互作用对内皮细胞产生多种作用。在本报告中，VPF/VEGF与人单核吞噬细胞（MPs）的相互作用进行了表征。辐射配体在4℃下的结合研究表明，存在一类单一的结合位点，kd约为300至500 pmol/L（比内皮细胞上的高亲和力结合位点[ECs]的亲和力低约20倍），其占据与VPF/ vegf诱导的MP迁移和组织因子的表达相关。这些结合结果与功能实验相一致，表明相同的VPF/VEGF制剂在刺激MP趋化性方面的效果比诱导EC增殖的效果低一个数量级。当表面结合125I-VPF/VEGF的MPs加热到37℃时，发生内吞和降解。VPF/VEGF结合位点的占据导致随后细胞内信号转导机制的激活，如MP细胞内钙浓度的增加所示。与125I-VPF/VEGF的交联研究显示了一个新的高分子量带（对应于假定的125I-VPF/VEGF受体复合物），其出现被过量未标记的VPF/VEGF阻断。与这些结果一致的是，暴露于VPF/VEGF的32po4标记的MPs的免疫沉淀显示出类似的单带流动性，而在未治疗的对照组中未见。这些结果表明，VPF/VEGF与MPs的相互作用虽然比与ECs的相互作用亲和力低，但也是多肽与特定细胞表面蛋白相互作用的结果，并导致细胞内转导机制的激活。
Vascular permeability factor/vascular endothelial growth factor (VPF/VEGF) is a polypeptide mediator, elaborated by certain tumors and other cell types, that exerts multiple effects on endothelium via interaction with a class of high-affinity binding sites. In this report, the interaction of VPF/VEGF with human mononuclear phagocytes (MPs) is characterized. Radioligand binding studies at 4 degrees C showed the presence of a single class of binding sites, kd approximately 300 to 500 pmol/L (approximately 20 times lower affinity than the high-affinity binding site on endothelial cells [ECs]), the occupancy of which correlated with VPF/VEGF-induced MP migration and expression of tissue factor. These binding results were paralleled by functional experiments which indicated that the same VPF/VEGF preparations were about an order of magnitude less effective in stimulating MP chemotaxis than in inducing EC proliferation. When MPs with surface-bound 125I-VPF/VEGF were warmed to 37 degrees C, endocytosis and degradation occurred. Occupancy of VPF/VEGF binding site resulted in subsequent activation of intracellular signal transduction mechanisms, as shown by an increase in MP intracellular calcium concentration. Cross-linking studies with 125I-VPF/VEGF showed a new high-molecular weight band (corresponding to putative 125I-VPF/VEGF-receptor complex), the appearance of which was blocked by excess unlabeled VPF/VEGF. Consistent with these results, immunoprecipitation of 32PO4-labeled MPs exposed to VPF/VEGF showed a single band of similar mobility, not seen in untreated controls. These results demonstrate that the interaction of VPF/VEGF with MPs, though of lower affinity than that observed with ECs, also results from interaction of the polypeptide with a specific cell-surface protein and leads to activation of intracellular transduction mechanisms.