The Vascular Endothelial Growth Factor Receptor Flt-1 Mediates Biological Activities
IMPLICATIONS FOR A FUNCTIONAL ROLE OF PLACENTA GROWTH FACTOR IN MONOCYTE ACTIVATION AND CHEMOTAXIS*
- Matthias Clauss‡§,
- Herbert Weich¶,
- Georg Breier‡,
- Ulrike Knies‡,
- Wolfgang Röckl¶,
- Johannes Waltenberger∥ and
- Werner Risau‡
- From the ‡ Abteilung für Molekulare Zellbiologie, Max-Planck-Institut für Physiologische und Klinische Forschung, D-61231 Bad Nauheim, Germany,
- ¶ Abteilung für Genexpression, Gesellschaft für Biotechnologische Forschung, D-38124 Braunschweig, Germany, and
- ∥ Abteilung Innere Medizin II, Medizinische Klinik und Poliklinik, Universität Ulm, D-89070 Ulm, Germany
- § To whom correspondence should be addressed. Fax: 49-6032-72259.
Abstract
Two distinct receptors for vascular endothelial growth factor (VEGF), the tyrosine kinase receptors Flt-1 and Flk-1/KDR, have been described. In this study we show that monocytes, in contrast to endothelium, express only the VEGF receptor Flt-1, and that this receptor specifically binds also the VEGF homolog placenta growth factor (PlGF). Both VEGF and PlGF stimulate tissue factor production and chemotaxis in monocytes at equivalent doses. In contrast, endothelial cells expressing both the Flt-1 and the Flk-1/KDR receptors produce more tissue factor upon stimulation with VEGF than after stimulation with PlGF. Neutralizing antibodies to the KDR receptor reduce the VEGF-stimulated tissue factor induction in endothelial cells to levels obtained by stimulation with PlGF alone, but do not affect PlGF-induced tissue factor induction in endothelial cells nor the VEGF-dependent tissue factor production in monocytes. These findings strongly suggest Flt-1 as a functional receptor for VEGF and PlGF in monocytes and endothelial cells and identify this receptor as a mediator of monocyte recruitment and procoagulant activity.
Footnotes
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↵* The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
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↵1 The abbreviations used are:
- VEGF
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vascular endothelial growth factor
- PlGF
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placenta growth factor
- RT-PCR
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reverse transcriptase-polymerase chain reaction
- PAE cells
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porcine aortic endothelial cells
- HUVE
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human umbilical vein endothelial cells.
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↵2 G. Breier, unpublished observation.
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↵3 P. Carmeliet, personal communication.
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- Received March 5, 1996.
- Revision received April 17, 1996.
- © 1996 by The American Society for Biochemistry and Molecular Biology, Inc.
