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

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, ex press only the VEGF receptor Flt-1, and that this receptor specificall y binds also the VEGF homolog placenta growth factor (PlGF). Both VEGF and PlGF stimulate tissue factor production and chemotaxis in monocyt es 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 facto r induction in endothelial cells to levels obtained by stimulation wit h PlGF alone, but do not affect PlGF-induced tissue factor induction i n endothelial cells nor the VEGF dependent tissue factor production in monocytes, These findings strongly suggest Flt-1 as a functional rece ptor for VEGF and PlGF in monocytes and endothelial cells and identify this receptor as a mediator of monocyte recruitment and procoagulant activity.