Witmer Antonella N, Dai Jiapei, Weich Herbert A, Vrensen Gijs F J M, Schlingemann Reinier O
Ocular Angiogenesis Group, Department of Ophthalmology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
J Histochem Cytochem. 2002 Jun;50(6):767-77. doi: 10.1177/002215540205000603.
The vascular endothelial growth factor (VEGF) family is involved in angiogenesis, and therefore VEGFs are considered as targets for anti-angiogenic therapeutic strategies against cancer. However, the physiological functions of VEGFs in quiescent tissues are unclear and may interfere with such systemic therapies. In pathological conditions, increased levels of expression of the VEGF receptors VEGFR-1, VEGFR-2, and VEGFR-3 accompany VEGF activity. In this study we investigated normal human and monkey tissues for expression patterns of these receptors. Immunohistochemical staining methods at the light and electron microscopic level were applied to normal human and monkey tissue samples, using monoclonal antibodies (MAbs) against the three VEGFRs and anti-endothelial MAbs PAL-E and anti-CD31 to identify blood and lymph vessels. In human and monkey, similar distribution patterns of the three VEGFRs were found. Co-expression of VEGFR-1, -2, and -3 was observed in microvessels adjacent to epithelia in the eye, gastrointestinal mucosa, liver, kidney, and hair follicles, which is in line with the reported preferential expression of VEGF-A in some of these epithelia. VEGFR-1, -2, and -3 expression was also observed in blood vessels and sinusoids of lymphoid tissues. Furthermore, VEGFR-1, but not VEGFR-2 and -3, was present in microvessels in brain and retina. Electron microscopy showed that VEGFR-1 expression was restricted to pericytes and VEGFR-2 to endothelial cells in normal vasculature of tonsils. These findings indicate that VEGFRs have specific distribution patterns in normal tissues, suggesting physiological functions of VEGFs that may be disturbed by systemic anti-VEGF therapy. One of these functions may be involvement of VEGF in paracrine relations between epithelia and adjacent capillaries.
血管内皮生长因子（VEGF）家族参与血管生成，因此VEGF被视为针对癌症的抗血管生成治疗策略的靶点。然而，VEGF在静止组织中的生理功能尚不清楚，可能会干扰此类全身治疗。在病理条件下，VEGF受体VEGFR-1、VEGFR-2和VEGFR-3表达水平的升高与VEGF活性相伴。在本研究中，我们调查了正常人类和猴子组织中这些受体的表达模式。使用针对三种VEGFR的单克隆抗体（MAb）以及抗内皮MAb PAL-E和抗CD31来识别血管和淋巴管，通过光镜和电镜水平的免疫组织化学染色方法对正常人类和猴子组织样本进行检测。在人类和猴子中，发现三种VEGFR具有相似的分布模式。在眼睛、胃肠道黏膜、肝脏、肾脏和毛囊中与上皮相邻的微血管中观察到VEGFR-1、-2和-3的共表达，这与报道的这些上皮中某些优先表达VEGF-A的情况一致。在淋巴组织的血管和血窦中也观察到VEGFR-1、-2和-3的表达。此外，VEGFR-1存在于脑和视网膜的微血管中，而VEGFR-2和-3则不存在。电子显微镜显示，在扁桃体的正常脉管系统中，VEGFR-1的表达仅限于周细胞，VEGFR-2的表达仅限于内皮细胞。这些发现表明VEGFR在正常组织中具有特定的分布模式，提示VEGF的生理功能可能会受到全身抗VEGF治疗的干扰。其中一个功能可能是VEGF参与上皮与相邻毛细血管之间的旁分泌关系。
