Dendritic cells derived from peripheral monocytes express endothelial markers and in the presence of angiogenic growth factors differentiate into endothelial-like cells

CD14-positive monocytes obtained from human peripheral blood were cultured with GM-CSF and IL-4. During the early culture phase immature dendritic cel ls (DCs) developed which not only expressed CD1a, HLA-DR and CD86, but also expressed the endothelial cell markers von Willebrand factor (vWF), VE-cad herin and VEGF receptors Flt-1 and Flt-4. Further maturation of DCs was ach ieved by prolonged cultivation with TNF alpha, These cells showed typical D C morphology and like professional antigen-presenting cells (APCs) expresse d CD83 and high levels of HLA-DR and CD86, However, if immature DCs were gr own with VEGF, bFGF and IGF-1 on fibronectin/vitronectin-coated culture dis hes, a marked change in morphology into caudated or oval cells occurred. In the presence of these angiogenic growth factors the cultured cells develop ed into endothelial-like cells (ELCs), characterized by increased expressio n of VWF, KDR and Flt-4 and a disappearance of CD1a and CD83. Addition of I L-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 w as responsible for the decrease in the expression of the DC markers CD1a an d 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 pr esence of specific cytokines immature DCs have the potential to differentia te along different lineages, i.e. into a cell type resembling ELCs.