Vascular endothelial growth factor inhibits the development of dendritic cells and dramatically affects the differentiation of multiple hematopoietic lineages in vivo
Vascular endothelial growth factor inhibits the development of dendritic cells and dramatically affects the differentiation of multiple hematopoietic lineages in vivo
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DOI：
10.1182/blood.v92.11.4150.423k45_4150_4166
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发表时间：
1998-12-01
期刊：
影响因子：
20.3
通讯作者：
Carbone, DP
中科院分区：
文献类型：
--
作者：
Gabrilovich, D;Ishida, T;Carbone, DP
最近描述了癌症中树突状细胞（DC）的功能缺陷，这可能代表肿瘤逃避免疫系统控制的机制之一。我们之前已经在体外证明，几乎所有肿瘤都会产生血管内皮生长因子（VEGF），它是导致这些细胞功能缺陷的肿瘤衍生因子之一。在这项研究中，我们研究了重组 VEGF 的体内输注是否可以重现观察到的 DC 功能障碍。以低至 50 ng/h 的速率连续输注 VEGF（导致血清 VEGF 浓度为 120 至 160 pg/mL），可显着抑制树突状细胞发育，并与 B 细胞和未成熟 Gr-1(+) 骨髓细胞的产生增加有关。 VEGF 的输注与骨髓祖细胞中转录因子 NF-κ B 活性的抑制有关。体外实验表明，VEGF 本身，而不是 VEGF 激活的内皮细胞释放的因子，影响多能干细胞，导致观察到的造血异常。这些数据表明，体内病理相关浓度的 VEGF 可能对多能干细胞产生影响，导致 DC 发育受阻并影响许多其他造血谱系。 (C) 1998 年，美国血液学会。
Defective function of dendritic cells (DC) in cancer has been recently described and may represent one of the mechanisms of tumor evasion from immune system control. We have previously shown in vitro that vascular endothelial growth factor (VEGF), produced by almost all tumors, is one of the tumor-derived factors responsible for the defective function of these cells. In this study, we investigated whether in vivo infusion of recombinant VEGF could reproduce the observed DC dysfunction. Continuous VEGF infusion, at rates as low as 50 ng/h (resulting in serum VEGF concentrations of 120 to 160 pg/mL), resulted in a dramatic inhibition of dendritic cell development, associated with an increase in the production of B cells and immature Gr-1(+) myeloid cells. Infusion of VEGF was associated with inhibition of the activity of the transcription factor NF-kappa B in bone marrow progenitor cells. Experiments in vitro showed that VEGF itself, and not factors released by VEGF-activated endothelial cells, affected polypotent stem cells resulting in the observed abnormal hematopoiesis. These data suggest that VEGF, at pathologically relevant concentrations in vivo, may exert effects on pluripotent stem cells that result in blocked DC development as well as affect many other hematopoietic lineages. (C) 1998 by The American Society of Hematology.