Characterization of vascular permeability factor/vascular endothelial growth factor receptors on mononuclear phagocytes

H. Shen, M. Clauss, J. Ryan, A. M. Schmidt, P. Tijburg, L. Borden, D. Connolly, D. Stern, J. Kao

Research output: Contribution to journalArticle

157 Scopus citations

Abstract

Vascular permeability factor/vascular endothelial growth factor (VPF/VEGF) is a polypeptide mediator, elaborated by certain tumors and other cell types, that exerts multiple effects on endothelium via interaction with a class of high-affinity binding sites. In this report, the interaction of VPF/VEGF with human mononuclear phagocytes (MPs) is characterized. Radioligand binding studies at 4°C showed the presence of a single class of binding sites, kd approximately 300 to 500 pmol/L (~20 times lower affinity than the high- affinity binding site on endothelial cells [ECs]), the occupancy of which correlated with VPF/VEGF-induced MP migration and expression of tissue factor. These binding results were paralleled by functional experiments which indicated that the same VPF/VEGF preparations were about an order of magnitude less effective in stimulating MP chemotaxis than in inducing EC proliferation. When MPs with surface-bound 125I-VPF/VEGF were warmed to 37°C, endocytosis and degradation occurred. Occupancy of VPF/VEGF binding site resulted in subsequent activation of intracellular signal transduction mechanisms, as shown by an increase in MP intracellular calcium concentration. Cross-linking studies with 125I-VPF/VEGF showed a new high- molecular weight band (corresponding to putative 125I-VPF/VEGF-receptor complex), the appearance of which was blocked by excess unlabeled VPF/VEGF. Consistent with these results, immunoprecipitation of 32PO4-labeled MPs exposed to VPF/VEGF showed a single band of similar mobility, not seen in untreated controls. These results demonstrate that the interaction of VPF/VEGF with MPs, though of lower affinity than that observed with ECs, also results from interaction of the polypeptide with a specific cell-surface protein and leads to activation of intracellular transduction mechanisms.

Original languageEnglish (US)
Pages (from-to)2767-2773
Number of pages7
JournalBlood
Volume81
Issue number10
DOIs
StatePublished - 1993

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

Fingerprint Dive into the research topics of 'Characterization of vascular permeability factor/vascular endothelial growth factor receptors on mononuclear phagocytes'. Together they form a unique fingerprint.

  • Cite this