Dendritic cells derived from peripheral monocytes express endothelial markers and in the presence of angiogenic growth factors differentiate into endothelial-like cells
Dendritic cells derived from peripheral monocytes express endothelial markers and in the presence of angiogenic growth factors differentiate into endothelial-like cells
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DOI：
10.1078/0171-9335-00136
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发表时间：
2001-01-01
影响因子：
6.6
通讯作者：
Havemann, K
中科院分区：
文献类型：
--
作者：
Pujol, BF;Lucibello, FC;Havemann, K
从人外周血中获取CD14阳性单核细胞，加入GM-CSF和IL-4进行培养。在培养早期形成的未成熟树突状细胞(DC)不仅表达CD1a、HLA-DR和CD86，还表达血管内皮细胞标志物von Willebrand因子(VWF)、VE-cadherin和VEGF受体Flt-1和Flt-4。用肿瘤坏死因子α长期培养的DC具有典型的DC形态，与专业抗原提呈细胞(APC)一样表达CD83和高水平的HLA-DR和CD86，但在纤维连接蛋白/玻璃体连接蛋白包被的培养皿中培养的未成熟DC，其形态发生了明显的变化，形成尾状或椭圆形细胞。在这些血管生长因子存在下，培养的细胞分化为内皮样细胞，其特征是VWF、KDR和Flt-4表达增加，CD1a和CD83消失。加入IL-4和肿瘤抑素M后，VE-钙粘附素的表达也增加，松散贴壁的细胞形成簇状、鹅卵石状和网状结构。表达VWF的ELCs主要来源于CD1a阳性的细胞，而表达CD1a和CD83的DC标志物CD83的表达下降与血管内皮生长因子有关。在混合白细胞培养中，成熟的DC比ELCs更具活性。此外，Ac-低密度脂蛋白的摄取和血浆基质上管状结构的形成仅限于ELCs。这些结果表明，在特定细胞因子存在的情况下，未成熟的DC有可能沿着不同的谱系分化，即分化为一种类似ELCs的细胞类型。
CD14-positive monocytes obtained from human peripheral blood were cultured with GM-CSF and IL-4. During the early culture phase immature dendritic cells (DCs) developed which not only expressed CD1a, HLA-DR and CD86, but also expressed the endothelial cell markers von Willebrand factor (vWF), VE-cadherin and VEGF receptors Flt-1 and Flt-4. Further maturation of DCs was achieved by prolonged cultivation with TNF alpha, These cells showed typical DC morphology and like professional antigen-presenting cells (APCs) expressed CD83 and high levels of HLA-DR and CD86, However, if immature DCs were grown with VEGF, bFGF and IGF-1 on fibronectin/vitronectin-coated culture dishes, a marked change in morphology into caudated or oval cells occurred. In the presence of these angiogenic growth factors the cultured cells developed into endothelial-like cells (ELCs), characterized by increased expression of VWF, KDR and Flt-4 and a disappearance of CD1a and CD83. Addition of IL-4 and Oncostatin M also increased VE-cadherin expression, and the loosely adherent cells formed clusters, cobblestones and network-like structures. vWF- expressing ELCs mainly originated from CD1a-positive cells, and VEGF was responsible for the decrease in the expression of the DC markers CD1a and CD83, In mixed leukocyte cultures, mature DCs were more potent APCs than ELCs. Moreover, Ac-LDL uptake, and the formation of tubular structures on a plasma matrix was restricted to ELCs. These results suggest that in the presence of specific cytokines immature DCs have the potential to differentiate along different lineages, i.e. into a cell type resembling ELCs.