Only a specific subset of human peripheral-blood monocytes has endothelial-like functional capacity.
The monocyte population in blood is considered a possible source of endothelial precursors. Because endothelial-specific receptor tyrosine kinases act as regulators of endothelial cell function, we investigated whether expression of the vascular endothelial growth factor receptor-2 (VEGFR-2) on monocytes is important for their endothelial-like functional capacity. Peripheral-blood monocytes expressing vascular endothelial growth factor receptor-2 (VEGFR-2), or CD14+/VEGFR-2+, were isolated, and their phenotypic, morphologic, and functional capacities were compared with those of monocytes negative for this marker (CD14+/VEGFR-2-). CD14+/VEGFR-2+ cells constituted approximately 2% +/- 0.5% of the total population of monocytes and 0.08% +/- 0.04% of mononuclear cells in blood. CD14+/VEGFR-2+ cells exhibited the potential to differentiate in vitro into cells with endothelial characteristics. The cells were efficiently transduced by a lentiviral vector driving expression of the green fluorescence protein (GFP). Transplantation of GFP-transduced cells into balloon-injured femoral arteries of nude mice significantly contributed to efficient reendothelialization. CD14+/VEGFR-2- did not exhibit any of these characteristics. These data demonstrate that the expression of VEGFR-2 on peripheral blood monocytes is essential for their endothelial-like functional capacity and support the notion of a common precursor for monocytic and endothelial cell lineage. Our results help clarify which subpopulations may restore damaged endothelium and may participate in the maintenance of vascular homeostasis.
Division of Transplantation Surgery, Karolinska Institutet, Karolinska University Hospital-Huddinge, Stockholm, Sweden.
Elzafir
E
Elsheikh
Mehmet
M
Uzunel
Zhong
Z
He
Jan
J
Holgersson
Grzegorz
G
Nowak
Suchitra
S
Sumitran-Holgersson
D000818:Animals; D015153:Blotting, Western; D002460:Cell Line; D019070:Cell Lineage; D002465:Cell Movement; D049109:Cell Proliferation; D002469:Cell Separation; D017690:Cell Transplantation; D004730:Endothelium, Vascular / Q000166:cytology*; D005263:Femoral Artery / Q000293:injuries; D005434:Flow Cytometry; D049452:Green Fluorescent Proteins / Q000378:metabolism; D006706:Homeostasis; D006801:Humans; D007150:Immunohistochemistry; D016086:Lentivirus / Q000235:genetics; D018950:Lipopolysaccharide Receptors / Q000096:biosynthesis; D051379:Mice; D008810:Mice, Inbred C57BL; D008819:Mice, Nude; D046529:Microscopy, Electron, Transmission; D008856:Microscopy, Fluorescence; D009000:Monocytes / Q000166:cytology*; D009389:Neovascularization, Pathologic; D018919:Neovascularization, Physiologic; D010641:Phenotype; D020133:Reverse Transcriptase Polymerase Chain Reaction; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000096:biosynthesis / Q000378:metabolism; D014945:Wound Healing
D018950:Lipopolysaccharide Receptors; D049452:Green Fluorescent Proteins; D040301:Vascular Endothelial Growth Factor Receptor-2