title: Flt-1, vascular endothelial growth factor receptor 1, is a novel cell surface marker for the lineage of monocyte-macrophages in humans.
abstract: 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 almost exclusively on vascular endothelial cells. As an exception, Flt-1 transcript was recently found to be expressed in human peripheral blood monocytes. However, the protein of the Flt-1 receptor on the cell surface of monocytes is yet to be identified, and whether the Flt-1 protein is expressed during the differentiation of monocyte-macrophage lineage cells has not been examined. Using monoclonal antibodies against 2 different antigenic epitopes on the Flt-1 extracellular domain, this study found that the major population 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 antibody significantly suppressed VEGF-induced migration of the monocytes, suggesting an important role for Flt-1 in the biologic function of monocytes. Furthermore, CD34+ cells in human cord blood, originally negative for the Flt-1 expression, differentiated into Flt-1+ cells in association with the appearance of monocyte-macrophage markers after a 2-week culture in the presence of hematopoietic cytokines. In addition, the Flt-1+ CD11b+ cell fraction from CD34+ cells was found to efficiently differentiate into multinuclear 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 molecule for monocyte-macrophage lineages in humans.
authors.affiliation: Department of Genetics and Department of Clinical Oncology, Institute of Medical Science, University of Tokyo, Japan.
authors.forename: A
authors.initials: A
authors.lastname: Sawano
authors.forename: S
authors.initials: S
authors.lastname: Iwai
authors.forename: Y
authors.initials: Y
authors.lastname: Sakurai
authors.forename: M
authors.initials: M
authors.lastname: Ito
authors.forename: K
authors.initials: K
authors.lastname: Shitara
authors.forename: T
authors.initials: T
authors.lastname: Nakahata
authors.forename: M
authors.initials: M
authors.lastname: Shibuya
mesh_terms: D016475:3T3 Cells; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D018952:Antigens, CD34 / Q000032:analysis; D015415:Biomarkers / Q000032:analysis; D002454:Cell Differentiation; D002460:Cell Line; D019070:Cell Lineage; D002633:Chemotaxis; D006412:Hematopoietic Stem Cells / Q000737:chemistry / Q000166:cytology / Q000378:metabolism; D006801:Humans; D016177:Macrophage-1 Antigen / Q000032:analysis; D008264:Macrophages / Q000378:metabolism*; D051379:Mice; D009000:Monocytes / Q000378:metabolism*; D010010:Osteoclasts / Q000166:cytology; D017434:Protein Structure, Tertiary; D011518:Proto-Oncogene Proteins / Q000276:immunology / Q000378:metabolism* / Q000502:physiology; D020794:Receptor Protein-Tyrosine Kinases / Q000276:immunology / Q000378:metabolism* / Q000502:physiology; D017978:Receptors, Growth Factor / Q000276:immunology / Q000378:metabolism / Q000502:physiology; D040262:Receptors, Vascular Endothelial Growth Factor; D040281:Vascular Endothelial Growth Factor Receptor-1
chemical_list: D000911:Antibodies, Monoclonal; D018952:Antigens, CD34; D015415:Biomarkers; D016177:Macrophage-1 Antigen; D011518:Proto-Oncogene Proteins; D017978:Receptors, Growth Factor; D020794:Receptor Protein-Tyrosine Kinases; D040262:Receptors, Vascular Endothelial Growth Factor; D040281:Vascular Endothelial Growth Factor Receptor-1