Delay of Spontaneous Neutrophil Apoptosis by Vascular Endothelial Growth Factor

ABSTRACT

PURPOSE: Vascular endothelial growth factor (VEGF) stimulates angiogenesis and vascular permeability. Tissue damage is related to angiogenesis, and induced by a delay in neutrophil apoptosis. This study was performed to investigate the effect of VEGF on the spontaneous neutrophil apoptosis via the activation of VEGFR-1 and phosphorylation of the p38-MAPK pathway. METHODS: Neutrophils were prepared from 10 healthy young donors, cultured for 20 h, and the apoptosis measured by the morphological changes and flow cytometry. The VEGF receptor expression and phosphorylation of mitogen activated protein kinase (MAPK) were measured using a Western blotting method. RESULTS: VEGF dose-dependently delayed the spontaneous neutrophil apoptosis, but this effect was blocked by pre-treatment of the cells with a VEGF receptor antagonist. VEGF increased the phosphorylated forms of the extracellular stress related kinase (Erk) and p38-MAPK. However, the VEGF-induced delay in apoptosis was not affected by the Erk inhibitor, PD98059 but was affected by the p38- MAPK inhibitor, SB203580. The VEGF receptor-1, but not the VEGF receptor-2, was detected in neutrophils, but its level was reduced in cultured neutrophils. CONCLUSION: VEGF delays neutrophil apoptosis through p38- MAPK activation.