Jakeman L B, Winer J, Bennett G L, Altar C A, Ferrara N
Department of Endocrine Research, Genentech, Inc., South San Francisco, California 94080.
J Clin Invest. 1992 Jan;89(1):244-53. doi: 10.1172/JCI115568.
Vascular endothelial growth factor (VEGF) is a secreted heparin-binding mitogen; its growth-promoting activity is limited to vascular endothelial cells in vitro and VEGF also stimulates angiogenesis in vivo. To identify target cells for VEGF and investigate the potential physiological role of this factor, iodinated recombinant human VEGF (125I-rhVEGF) was used for in vitro ligand autoradiography on tissue sections from adult rats. 125I-rhVEGF exhibited saturable, displaceable binding to a single class of sites with high affinity and low capacity in all tissues and organs examined. Colocalization of 125I-rhVEGF binding with Factor VIII-like immunoreactivity demonstrated binding sites associated with vascular endothelial cells of both fenestrated and nonfenestrated microvessels and the endothelium of large vessels, while no displaceable binding was evident on nonendothelial cells. Specific binding was associated with quiescent as well as proliferating vessels. These findings support the hypothesis that VEGF plays a specific role in both the maintenance and in the induction of growth of vascular endothelial cells.
血管内皮生长因子(VEGF)是一种分泌型肝素结合有丝分裂原;其促生长活性在体外仅限于血管内皮细胞,并且VEGF在体内也能刺激血管生成。为了确定VEGF的靶细胞并研究该因子的潜在生理作用,碘化重组人VEGF(125I-rhVEGF)被用于对成年大鼠组织切片进行体外配体放射自显影。在所有检测的组织和器官中,125I-rhVEGF都表现出与一类位点的可饱和、可置换结合,具有高亲和力和低容量。125I-rhVEGF结合与VIII因子样免疫反应性的共定位表明,结合位点与有孔和无孔微血管的血管内皮细胞以及大血管的内皮相关,而非内皮细胞上没有明显的可置换结合。特异性结合与静止以及增殖的血管相关。这些发现支持了VEGF在血管内皮细胞生长的维持和诱导中都发挥特定作用的假说。