A novel function for dendritic cell: clearance of VEGF via VEGF receptor-1.
It has been reported that the plasma levels of VEGF in tumor patients decreased during dendritic cell (DC)-based immunotherapy, but the underlying mechanism remains unclear. Our current report demonstrates that VEGF levels were significantly decreased in the supernatants of DCs incubated with rhVEGF or tumor conditioned medium (TCM) while the intracellular VEGF in DCs was increased. The increased intracellular VEGF was not due to the de novo VEGF synthesis by DCs because exogenous VEGF inhibited the mRNA expression of VEGF in DCs. More direct evidence was provided to demonstrate that Cy3-labeled VEGF could be internalized by DCs specifically and efficiently. In addition, the activity of DCs to internalize VEGF was abolished by neutralizing antibody against VEGF receptor-1 (Flt-1) and inhibitors of endocytosis such as carbonyl cyanide m-chlorophenyl hydrazone (CCCP) and genistein. This study highlights a novel function of DCs and allows a better understanding of the DC-VEGF interaction.
Xie
Yi
Y
Department of Surgery, The University of Hong Kong, Hong Kong SAR, China.
Fan
Jianqing
J
Chen
Juhua
J
Huang
Fang-Ping
FP
Cao
Brian
B
Tam
Paul K H
PK
Ren
Yi
Y
D045744:Cell Line, Tumor; D003188:Composite Resins / Q000494:pharmacology; D017077:Culture Media, Conditioned / Q000378:metabolism; D003713:Dendritic Cells / Q000187:drug effects / Q000378:metabolism*; D004705:Endocytosis / Q000187:drug effects; D006801:Humans; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism* / Q000494:pharmacology; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000037:antagonists & inhibitors / Q000378:metabolism*
D003188:Composite Resins; D017077:Culture Media, Conditioned; D042461:Vascular Endothelial Growth Factor A; C029597:Concise-Cap-C-Rynge; C501162:FLT1 protein, human; D040281:Vascular Endothelial Growth Factor Receptor-1