Ultrastructural localization of the vascular permeability factor/vascular endothelial growth factor (VPF/VEGF) receptor-2 (FLK-1, KDR) in normal mouse kidney and in the hyperpermeable vessels induced by VPF/VEGF-expressing tumors and adenoviral vectors

Vascular permeability factor/vascular endothelial growth factor (VPF/VEGF) interacts with two high-affinity tyrosine kinase receptors, VEGFR-1 and VEG FR-2, to increase microvascular permeability and induce angiogenesis. Both receptors are selectively expressed by vascular endothelial cells and are s trikingly increased in tumor vessels. We used a specific antibody to locali ze VEGFR-2 (FLK-1. KDR) in microvascular endothelium of normal mouse kidney s and in the microvessels induced by the TA3/St mammary tumor or by infecti on with an adenoviral vector engineered to express VPF/VEGF. A pre-embeddin g method was employed at the light and electron microscopic levels using ei ther nanogold or peroxidase as reporters. Equivalent staining was observed on both the luminal and abluminal surfaces of tumor- and adenovirus-induced vascular endothelium, but plasma membranes at interendothelial junctions w ere spared except at sites connected to vesiculovacuolar organelles (VVOs). VEGFR-2 was also localized to the membranes and stomatal diaphragms of som e VVOs. This staining distribution is consistent with a model in which VPF/ VEGF increases microvascular permeability by opening VVOs to allow the tran sendothelial cell passage of plasma and plasma proteins.