PUBLICATION

Tissue macrophages act as cellular chaperones for vascular anastomosis downstream of VEGF-mediated endothelial tip cell induction

Authors
Fantin, A., Vieira, J.M., Gestri, G., Denti, L., Schwarz, Q., Prykhozhij, S., Peri, F., Wilson, S.W., and Ruhrberg, C.
ID
ZDB-PUB-100427-3
Date
2010
Source
Blood   116(5): 829-840 (Journal)
Registered Authors
Gestri, Gaia, Peri, Francesca, Wilson, Steve
Keywords
none
MeSH Terms
  • Animals
  • Cell Polarity
  • Endothelial Cells/drug effects
  • Endothelial Cells/physiology
  • Endothelial Cells/ultrastructure
  • Endothelium, Vascular/growth & development
  • Female
  • Gene Knock-In Techniques
  • Macrophage Colony-Stimulating Factor/deficiency
  • Macrophage Colony-Stimulating Factor/genetics
  • Macrophage Colony-Stimulating Factor/physiology
  • Macrophages/physiology*
  • Male
  • Mice
  • Mice, Knockout
  • Neovascularization, Physiologic/drug effects*
  • Neovascularization, Physiologic/physiology
  • Neuropilin-1/physiology
  • Proto-Oncogene Proteins/deficiency
  • Receptor Protein-Tyrosine Kinases/physiology
  • Receptor, TIE-2
  • Retinal Vessels/growth & development
  • Rhombencephalon/blood supply*
  • Rhombencephalon/embryology
  • Trans-Activators/deficiency
  • Vascular Endothelial Growth Factor A/deficiency
  • Vascular Endothelial Growth Factor A/genetics
  • Vascular Endothelial Growth Factor A/physiology*
  • Yolk Sac/cytology
  • Zebrafish/embryology
PubMed
20404134 Full text @ Blood
Abstract
Blood vessel networks expand in a two-step process that begins with vessel sprouting and is followed by vessel anastomosis. Vessel sprouting is induced by chemotactic gradients of the vascular endothelial growth factor VEGF, which stimulates tip cell protrusion. Yet, it is not known which factors promote the fusion of neighbouring tip cells to add new circuits to the existing vessel network. By combining the analysis of mouse mutants defective in macrophage development or VEGF signalling with live imaging in zebrafish, we now show that macrophages promote tip cell fusion downstream of VEGF-mediated tip cell induction. Macrophages therefore play a hitherto unidentified and unexpected role as vascular fusion cells. Moreover, we show that there are striking molecular similarities between the pro-angiogenic tissue macrophages essential for vascular development and those that promote the angiogenic switch in cancer, including the expression of the cell surface proteins TIE2 and NRP1. Our findings suggest that tissue macrophages are a target for anti-angiogenic therapies, but that they could equally well be exploited to stimulate tissue vascularisation in ischemic disease.
Genes / Markers
Figures
Expression
Phenotype
Mutation and Transgenics
Human Disease / Model Data
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping
Errata and Notes