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

Dian Feng, Janice A. Nagy, Rolf A. Brekken, Anna Pettersson, Eleanor J. Manseau, Kathryn Pyne, Richard Mulligan, Philip E. Thorpe, Harold F. Dvorak, Ann M. Dvorak

Research output: Contribution to journalArticle

103 Scopus citations

Abstract

Vascular permeability factor/vascular endothelial growth factor (VPF/VEGF) interacts with two high-affinity tyrosine kinase receptors, VEGFR- 1 and VEGFR-2, to increase microvascular permeability and induce angiogenesis. Both receptors are selectively expressed by vascular endothelial cells and are strikingly increased in tumor vessels. We used a specific antibody to localize VEGFR-2 (FLK-1, KDR) in microvascular endothelium of normal mouse kidneys and in the microvessels induced by the TA3/St mammary tumor or by infection with an adenoviral vector engineered to express VPF/VEGF. A pre-embedding method was employed at the light and electron microscopic levels using either 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 were spared except at sites connected to vesiculovacuolar organelles (VVOs). VEGFR-2 was also localized to the membranes and stomatal diaphragms of some VVOs. This staining distribution is consistent with a model in which VPF/VEGF increases microvascular permeability by opening VVOs to allow the transendothelial cell passage of plasma and plasma proteins.

Original languageEnglish (US)
Pages (from-to)545-555
Number of pages11
JournalJournal of Histochemistry and Cytochemistry
Volume48
Issue number4
DOIs
StatePublished - Apr 2000

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Keywords

  • (VVO)
  • Endothelial cells
  • Fetal liver kinase 1 (Flk-1)
  • Kinase insert domain- containing receptor (KDR)
  • Mouse kidney
  • Tumor vessels
  • Ultrastructure immunocytochemistry
  • Vascular endothelial growth factor (VEGF)
  • Vascular endothelial growth factor receptor (VEGFR)
  • Vascular permeability factor (VPF)
  • Vascular permeability factor receptor (VPFR)
  • Vesiculovacuolar organelle

ASJC Scopus subject areas

  • Anatomy
  • Histology

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