Migration of human monocytes in response to vascular endothelial growth factor (VEGF) is mediated via the VEGF receptor flt-1

Bernhard Barleon, Silvano Sozzani, Dan Zhou, Herbert A. Weich, Alberto Mantovani, Dieter Marmé

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Abstract

Treatment of human monocytes with vascular endothelial growth factor (VEGF) isolated from tumor cell supernatants was reported to induce monocyte activation and migration. In this study we show that recombinant human VEGF 165 and VEGF 121 had a maximal effect on human monocyte migration at 65 to 250 pmol/L. Chemotactic activity of VEGF 165 was inhibited by a specific antiserum against VEGF, by heat treatment of VEGF 165, and by protein kinase inhibitors. In addition, we could show that VEGF-stimulated monocyte migration is mediated by a pertussis toxin-sensitive GTP-binding protein. Placenta growth factor (PIGF 152), a heparin-binding growth factor related to VEGF, was also chemotactic for monocytes at concentrations between 2.5 and 25 pmol/L. In accordance with these findings, human monocytes showed specific and saturable binding for 125I-VEGF 165 (half-maximal binding at 1 to 1.5 nmol/L). Using Northern blot analysis, we further could show that human monocytes express only the gene for the VEGF receptor type, flt-1, but not for the second known VEGF receptor, KDR. Resting monocytes expressed low levels of flt-1 gene only. Brief exposure (2 to 4 hours) of human monocytes to lipopolysaccharids, a prototypic monocyte activator, led to a significant upregulation of the flt-1 mRNA level. The results presented here suggest that monocyte chemotaxis in response to VEGF and most likely to PIGF 152 is mediated by flt-1 and thus show a possible function for the VEGF-receptor flt-1.

Original languageEnglish
Pages (from-to)3336-3343
Number of pages8
JournalBlood
Volume87
Issue number8
Publication statusPublished - Apr 15 1996

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Vascular Endothelial Growth Factor Receptor-1
Vascular Endothelial Growth Factor Receptor
Vascular Endothelial Growth Factor A
Monocytes
Intercellular Signaling Peptides and Proteins
Genes
Pertussis Toxin
Protein Kinase Inhibitors
GTP-Binding Proteins
Heparin
Tumors
Immune Sera
Chemical activation
Heat treatment
Cells
human VEGFA protein
Messenger RNA
Chemotaxis
Northern Blotting
Up-Regulation

ASJC Scopus subject areas

  • Hematology

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Migration of human monocytes in response to vascular endothelial growth factor (VEGF) is mediated via the VEGF receptor flt-1. / Barleon, Bernhard; Sozzani, Silvano; Zhou, Dan; Weich, Herbert A.; Mantovani, Alberto; Marmé, Dieter.

In: Blood, Vol. 87, No. 8, 15.04.1996, p. 3336-3343.

Research output: Contribution to journalArticle

Barleon, Bernhard ; Sozzani, Silvano ; Zhou, Dan ; Weich, Herbert A. ; Mantovani, Alberto ; Marmé, Dieter. / Migration of human monocytes in response to vascular endothelial growth factor (VEGF) is mediated via the VEGF receptor flt-1. In: Blood. 1996 ; Vol. 87, No. 8. pp. 3336-3343.
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