Circulating monocytes expressing CD31: implications for acute and chronic angiogenesis.
To identify the roles of various circulating cells (eg, endothelial and/or stem and progenitor cells) in angiogenesis, we parabiosed a wild-type syngeneic mouse with a transgenic syngeneic green fluorescent protein mouse. Following the establishment of a common circulation between these parabionts, we investigated acute (7 to 10 days), subacute (2 to 3 weeks), and chronic (4 to 6 weeks) phases of angiogenesis in wild-type mice using wound healing, implanted gel foam fragments, and subcutaneous tumor assays, respectively. We found that under in vitro conditions, circulating murine monocytes expressed F4/80, CD31, and vascular endothelial growth factor receptor 2, but neither CD133 nor von Willebrand factor, whereas murine endothelial cells expressed CD31, vascular endothelial growth factor receptor 2, and von Willebrand factor, but neither CD133 nor F4/80. Immunofluorescence analysis revealed that green fluorescent protein-positive cells in the walls of new vessels in wounds, gel foam blocks, and tumors expressed both F4/80 and CD31, that is, macrophages. Pericytes, cells that express both CD31 and desmin, were found both in the walls of tumor-associated vessels and within tumors. Collectively, these data demonstrate that monocytes (ie, cells that express both CD31 and F4/80) may be recruited to the site of tissue injury and directly contribute to angiogenesis, reaffirming the close relationships between various cell types within the reticuloendothelial system and suggesting possible targets for anticancer treatments.
Department of Cancer Biology, Cancer MetastasisResearch Center, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA.
Sun-Jin
SJ
Kim
Jang-Seong
JS
Kim
John
J
Papadopoulos
Seung
S
Wook Kim
Marva
M
Maya
Fahao
F
Zhang
Junquin
J
He
Dominic
D
Fan
Robert
R
Langley
Isaiah J
IJ
Fidler
D000071916:AC133 Antigen; D000208:Acute Disease; D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D000943:Antigens, Differentiation / Q000378:metabolism; D002908:Chronic Disease; D004730:Endothelium, Vascular / Q000502:physiology*; D005260:Female; D005455:Fluorescent Antibody Technique; D006023:Glycoproteins / Q000378:metabolism; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D008264:Macrophages / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D055017:Monocyte-Macrophage Precursor Cells / Q000502:physiology*; D009000:Monocytes / Q000378:metabolism*; D009369:Neoplasms / Q000098:blood supply*; D009360:Neoplastic Cells, Circulating / Q000378:metabolism*; D009389:Neovascularization, Pathologic / Q000378:metabolism*; D010455:Peptides / Q000378:metabolism; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000378:metabolism*; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000378:metabolism; D014945:Wound Healing; D014841:von Willebrand Factor / Q000378:metabolism
D000071916:AC133 Antigen; D015703:Antigens, CD; D000943:Antigens, Differentiation; D006023:Glycoproteins; D010455:Peptides; D019408:Platelet Endothelial Cell Adhesion Molecule-1; C000606024:Prom1 protein, mouse; C036763:monocyte-macrophage differentiation antigen; D014841:von Willebrand Factor; D049452:Green Fluorescent Proteins; D040301:Vascular Endothelial Growth Factor Receptor-2