A. Sawano et al., Flt-1, vascular endothelial growth factor receptor 1, is a novel cell surface marker for the lineage of monocyte-macrophages in humans, BLOOD, 97(3), 2001, pp. 785-791
Flt-1, also known as vascular endothelial growth factor receptor 1 (VEGFR-1
), is a high-affinity tyrosine kinase receptor for VEGF and is expressed al
most exclusively on vascular endothelial cells. As an exception, Flt-1 tran
script was recently found to be expressed in human peripheral blood monocyt
es, However, the protein of the Flt-1 receptor on the cell surface of monoc
ytes is yet to be identified, and whether the Flt-1 protein is expressed du
ring the differentiation of monocyte-macrophage lineage cells has not been
examined. Using monoclonal antibodies against 2 different antigenic epitope
s on the Flt-1 extracellular domain, this study found that the major popula
tion of the monocyte-marker CD97(+) cells in human peripheral blood express
Flt-1 as a cell surface molecule. VEGFR-2 (KDR/Flk-1) was not expressed at
detectable levels in these cells. An Flt-1 neutralizing monoclonal antibod
y significantly suppressed VEGF-induced migration of the monocytes, suggest
ing an important role for Flt-1 in the biologic function of monocytes, Furt
hermore, CD34(+) cells in human cord blood, originally negative for the Flt
-1 expression, differentiated into Flt-1(+) cells in association with the a
ppearance of monocyte-macrophage markers after a 5-week culture in the pres
ence of hematopoietic cytokines, In addition, the Flt-1(+)CD11b(+) cell fra
ction from CD34(+) cells was found to efficiently differentiate into multin
uclear osteoclasts in the presence of macrophage colony-stimulating factor
and osteoclast differentiation factor. These results strongly suggest that
Flt-1 is a novel cell Surface marker as well as a biologically functional m
olecule for monocyte-macrophage lineages in humans. (C) 2001 by The America
n Society of Hematology.