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 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 TNFalpha. 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.
Fernandez Pujol
B
B
Institute of Molecular Biology and Tumor Research, University of Marburg, Germany.
Lucibello
F C
FC
Zuzarte
M
M
Lütjens
P
P
Müller
R
R
Havemann
K
K
D015703:Antigens, CD; D018949:Antigens, CD1 / Q000378:metabolism; D015415:Biomarkers; D001777:Blood Coagulation; D015820:Cadherins / Q000096:biosynthesis*; D002454:Cell Differentiation; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D018920:Coculture Techniques; D003713:Dendritic Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D016228:Endothelial Growth Factors / Q000494:pharmacology; D004727:Endothelium; D016326:Extracellular Matrix Proteins / Q000096:biosynthesis*; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology; D015847:Interleukin-4 / Q000494:pharmacology; D018950:Lipopolysaccharide Receptors / Q000378:metabolism; D008222:Lymphokines / Q000494:pharmacology; D009000:Monocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D053683:Oncostatin M; D010455:Peptides / Q000494:pharmacology; D020794:Receptor Protein-Tyrosine Kinases / Q000096:biosynthesis*; D017978:Receptors, Growth Factor / Q000096:biosynthesis*; D042461:Vascular Endothelial Growth Factor A; D040281:Vascular Endothelial Growth Factor Receptor-1; D040321:Vascular Endothelial Growth Factor Receptor-3; D042442:Vascular Endothelial Growth Factors; D014841:von Willebrand Factor / Q000096:biosynthesis*; D000099152:Cadherin 5
D015703:Antigens, CD; D018949:Antigens, CD1; D015415:Biomarkers; D015820:Cadherins; D016228:Endothelial Growth Factors; D016326:Extracellular Matrix Proteins; D016222:Fibroblast Growth Factor 2; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D007334:Insulin-Like Growth Factor I; D015847:Interleukin-4; D018950:Lipopolysaccharide Receptors; D008222:Lymphokines; D053683:Oncostatin M; D010455:Peptides; D020794:Receptor Protein-Tyrosine Kinases; D017978:Receptors, Growth Factor; D042461:Vascular Endothelial Growth Factor A; D040281:Vascular Endothelial Growth Factor Receptor-1; D040321:Vascular Endothelial Growth Factor Receptor-3; D042442:Vascular Endothelial Growth Factors; D014841:von Willebrand Factor; D000099152:Cadherin 5; C419393:CD1a antigen; C508351:OSM protein, human; C501162:FLT1 protein, human