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

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

Research output: Contribution to journalArticle

156 Citations (Scopus)

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 parallelled 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
StatePublished - May 15 1993
Externally publishedYes

Fingerprint

Vascular Endothelial Growth Factor Receptor
Phagocytes
Vascular Endothelial Growth Factor A
Endothelial cells
Binding Sites
Endothelial Cells
Chemical activation
Signal transduction
Peptides

ASJC Scopus subject areas

  • Hematology

Cite this

Shen, H., Clauss, M., Ryan, J., Schmidt, A. M., Tijburg, P., Borden, L., ... Kao, J. (1993). Characterization of vascular permeability factor/vascular endothelial growth factor receptors on mononuclear phagocytes. Blood, 81(10), 2767-2773.

Characterization of vascular permeability factor/vascular endothelial growth factor receptors on mononuclear phagocytes. / Shen, H.; Clauss, Matthias; Ryan, J.; Schmidt, A. M.; Tijburg, P.; Borden, L.; Connolly, D.; Stern, D.; Kao, J.

In: Blood, Vol. 81, No. 10, 15.05.1993, p. 2767-2773.

Research output: Contribution to journalArticle

Shen, H, Clauss, M, Ryan, J, Schmidt, AM, Tijburg, P, Borden, L, Connolly, D, Stern, D & Kao, J 1993, 'Characterization of vascular permeability factor/vascular endothelial growth factor receptors on mononuclear phagocytes', Blood, vol. 81, no. 10, pp. 2767-2773.
Shen, H. ; Clauss, Matthias ; Ryan, J. ; Schmidt, A. M. ; Tijburg, P. ; Borden, L. ; Connolly, D. ; Stern, D. ; Kao, J. / Characterization of vascular permeability factor/vascular endothelial growth factor receptors on mononuclear phagocytes. In: Blood. 1993 ; Vol. 81, No. 10. pp. 2767-2773.
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