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.
Elsheikh
Elzafir
E
Division of Transplantation Surgery, Karolinska Institutet, Karolinska University Hospital-Huddinge, Stockholm, Sweden.
Uzunel
Mehmet
M
He
Zhong
Z
Holgersson
Jan
J
Nowak
Grzegorz
G
Sumitran-Holgersson
Suchitra
S
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