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 language | English |
|---|---|
| Pages (from-to) | 3336-3343 |
| Number of pages | 8 |
| Journal | Blood |
| Volume | 87 |
| Issue number | 8 |
| Publication status | Published - Apr 15 1996 |
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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 journal › Article
}
TY - JOUR
T1 - Migration of human monocytes in response to vascular endothelial growth factor (VEGF) is mediated via the VEGF receptor flt-1
AU - Barleon, Bernhard
AU - Sozzani, Silvano
AU - Zhou, Dan
AU - Weich, Herbert A.
AU - Mantovani, Alberto
AU - Marmé, Dieter
PY - 1996/4/15
Y1 - 1996/4/15
N2 - 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.
AB - 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.
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M3 - Article
VL - 87
SP - 3336
EP - 3343
JO - Blood
JF - Blood
SN - 0006-4971
IS - 8
ER -