Effects of vascular endothelial growth factor on differentiation and function o f dendritic cells generated from CD34~+ hematopoietic progenito r cells in vitro

Objective To investigate the effects of vascular endothelial growth factor (VEGF) on diffe rentiation and function of dendritic cells derived from CD34 + hematopoieti c progenitor cells. Methods After isolation from umbilical cord blo od with a high-gradient magnetic cell sorting system (MACS), the CD34 + ce lls were cultured with a cocktail cytokines for differentiating into dendritic cells (DC) . The cells were stimulated by VEGF (25 ng/ml) either at the beginni ng or at day 9 of culture. Kinetics analysis of cell proliferation was performe d during the process of cell culture, and the expression of DC differentiation a ntigens including CD1α, CD83, CD80, CD54 and HLA-DR was examined by flow cytom etry. DC function was evaluated by the ability to induce proliferation of allog eneic T cells in mixed lymphocyte reaction (MLR) assay, and the productio n of IL-12 by ELISA. Results VEGF added at day 1 of culture induc ed an increase of total cell numbers by (1.51 ± 0.23)-folds (P=0 .001). VEGF added at the initial but not the late stage of culture could drama tically down-regulate the expression of CD1a \vs (8 1.20±6.93)%\])%\], CD83 \vs (87.98± 7.97)%\], CD80 (42.93±1.32)% vs (94.53±0.87)%\], and HLA-DR vs ( 74.15±3.74)%\],while obviously up-regulate the expression o f CD14. Moreover, the inhibitory effect of VEGF on DC function was confirmed by a reduced ability to induce proliferation of allogeneic T cells and production o f IL-12 (P0.01). Conclusions VEGF could induce the ex pansion of hematopoietic progenitor cells and inhibit at the early stage their d ifferentiation into mature DC.