title: Migration of human monocytes in response to vascular endothelial growth factor (VEGF) is mediated via the VEGF receptor flt-1.
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 VEGF165, and VEGF121 had a maximal effect on human monocyte migration at 65 to 250 pmol/L. Chemotactic activity of VEGF165 was inhibited by a specific antiserum against VEGF, by heat treatment of VEGF165, 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 (PlGF152), 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-VEGF165 (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 lipopolysaccharide, 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 PlGF152 is mediated by flt-1 and thus show a possible function for the VEGF-receptor flt-1.
authors.affiliation: Institute of Molecular Medicine, Tumor Biology Center Freiburg, Germany.
authors.forename: B
authors.initials: B
authors.lastname: Barleon
authors.forename: S
authors.initials: S
authors.lastname: Sozzani
authors.forename: D
authors.initials: D
authors.lastname: Zhou
authors.forename: H A
authors.initials: HA
authors.lastname: Weich
authors.forename: A
authors.initials: A
authors.lastname: Mantovani
authors.forename: D
authors.initials: D
authors.lastname: Marmé
mesh_terms: D001667:Binding, Competitive; D002634:Chemotaxis, Leukocyte / Q000187:drug effects / Q000502:physiology*; D016228:Endothelial Growth Factors / Q000494:pharmacology*; D004730:Endothelium, Vascular / Q000166:cytology; D019204:GTP-Binding Proteins / Q000502:physiology; D006801:Humans; D008222:Lymphokines / Q000494:pharmacology*; D009000:Monocytes / Q000187:drug effects*; D009130:Muscle, Smooth / Q000166:cytology; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D009504:Neutrophils / Q000187:drug effects / Q000502:physiology; D037342:Pertussis Toxin; D000072483:Placenta Growth Factor; D011257:Pregnancy Proteins / Q000737:chemistry / Q000494:pharmacology; D011518:Proto-Oncogene Proteins / Q000187:drug effects / Q000502:physiology*; D020794:Receptor Protein-Tyrosine Kinases / Q000187:drug effects / Q000502:physiology*; D017978:Receptors, Growth Factor / Q000502:physiology; D040262:Receptors, Vascular Endothelial Growth Factor; D011994:Recombinant Proteins / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*; D042461:Vascular Endothelial Growth Factor A; D040281:Vascular Endothelial Growth Factor Receptor-1; D042442:Vascular Endothelial Growth Factors; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
chemical_list: D016228:Endothelial Growth Factors; D008222:Lymphokines; C000608036:PGF protein, human; D011257:Pregnancy Proteins; D011518:Proto-Oncogene Proteins; D017978:Receptors, Growth Factor; D011994:Recombinant Proteins; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D010566:Virulence Factors, Bordetella; D000072483:Placenta Growth Factor; D009240:N-Formylmethionine Leucyl-Phenylalanine; D037342:Pertussis Toxin; D020794:Receptor Protein-Tyrosine Kinases; D040262:Receptors, Vascular Endothelial Growth Factor; D040281:Vascular Endothelial Growth Factor Receptor-1; D019204:GTP-Binding Proteins