Flt-1, vascular endothelial growth factor receptor 1, is a novel cell surface marker for the lineage of monocyte-macrophages in humans

• Published in: Blood Vol. 97; no. 3; pp. 785 - 791
• Main Authors: Sawano, Asako, Iwai, Shinobu, Sakurai, Yoshiko, Ito, Mikito, Shitara, Kenya, Nakahata, Tatsutoshi, Shibuya, Masabumi
• Format: Journal Article
• Language: English
• Published: Washington, DC Elsevier Inc 01-02-2001; The Americain Society of Hematology
• Subjects: 3T3 Cells; Animals; Antibodies, Monoclonal - immunology; Antigens, CD34 - analysis; Biological and medical sciences; Biomarkers - analysis; Cell Differentiation; Cell Line; Cell Lineage; Chemotaxis; Combined treatment; Hematopoietic Stem Cells - chemistry; Hematopoietic Stem Cells - cytology; Hematopoietic Stem Cells - metabolism; Humans; Macrophage-1 Antigen - analysis; Macrophages - metabolism; Medical sciences; Mice; Monocytes - metabolism; Osteoclasts - cytology; Protein Structure, Tertiary; Proto-Oncogene Proteins - immunology; Proto-Oncogene Proteins - metabolism; Proto-Oncogene Proteins - physiology; Receptor Protein-Tyrosine Kinases - immunology; Receptor Protein-Tyrosine Kinases - metabolism; Receptor Protein-Tyrosine Kinases - physiology; Receptors, Growth Factor - immunology; Receptors, Growth Factor - metabolism; Receptors, Growth Factor - physiology; Receptors, Vascular Endothelial Growth Factor; Treatment. General aspects; Tumors; Vascular Endothelial Growth Factor Receptor-1; Human; Monocyte; Stem cell; Hematopoietic cell; Biological marker; Cell lineage; Cell differentiation; Membrane receptor; Vascular endothelium growth factor; Hematopoiesis; Progenitor cell; Macrophage; Biological receptor; Vascular endothelial growth factor receptor 1
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood.V97.3.785

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.