In vitro effects of angiopoietins and VEGF on hematopoietic and endothelial cells.
To investigate the role of TIE-2/angiopoietins (Angs) in postnatal hematopoiesis, we cultured bone marrow cells in the presence of Ang-1 and -2 with or without VEGF. While either Ang-1 or Ang-2 alone had hematopoietic effects on unseparated bone marrow cells and no effect on proliferation of endothelial cells, both enhanced the growth of endothelial cells and hematopoietic progenitor cells in the presence of VEGF. FACS analysis showed that Lin(-)TIE-2(+)Flk-1(+) cells cocultured with OP9 stromal cells gave rise to endothelial and hematopoietic cells in the presence of VEGF and Ang-1. Ang-1 promoted the adhesion of sorted primary Lin(-)TIE-2(+) cells to fibronectin, and this adhesion enhanced proliferation of hematopoietic progenitor cells synergistically with stem cell factor (SCF). Our findings suggest that TIE-2/angiopoietins may act as critical regulators of proliferation of hematopoietic progenitors and endothelial cells in a synergistic manner.
Huang
X L
XL
Institute of Molecular Embryology and Genetics (IMEG), Kumamoto University School of Medicine, 2-2-1 Honjo, Kumamoto, 860-0811, Japan.
Takakura
N
N
Suda
T
T
D042683:Angiopoietin-1; D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology / Q000187:drug effects*; D002448:Cell Adhesion / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D004357:Drug Synergism; D016228:Endothelial Growth Factors / Q000494:pharmacology*; D004727:Endothelium / Q000166:cytology; D005353:Fibronectins / Q000378:metabolism; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000187:drug effects*; D008222:Lymphokines / Q000494:pharmacology*; D008562:Membrane Glycoproteins / Q000494:pharmacology*; D051379:Mice; D008810:Mice, Inbred C57BL; D020794:Receptor Protein-Tyrosine Kinases / Q000378:metabolism; D042787:Receptor, TIE-2; D019089:Stem Cell Factor / Q000494:pharmacology; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
D042683:Angiopoietin-1; C467628:Angpt1 protein, mouse; D016228:Endothelial Growth Factors; D005353:Fibronectins; D008222:Lymphokines; D008562:Membrane Glycoproteins; D019089:Stem Cell Factor; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D020794:Receptor Protein-Tyrosine Kinases; D042787:Receptor, TIE-2