To investigate the role of TIE-2/angiopoietins (Angs) in postnatal hematopo
iesis, we cultured bone marrow cells in the presence of Ang-1 and -2 with o
r without VEGF, While either Ang-1 or Ang-2 alone had hematopoietic effects
on unseparated bone marrow cells and no effect on proliferation of endothe
lial cells, both enhanced the growth of endothelial cells and hematopoietic
progenitor cells in the presence of VEGF. FAGS analysis showed that Lin(-)
TIE-2(+)Flk-1(+) cells cocultured with OP9 stromal cells gave rise to endot
helial and hematopoietic cells in the presence of VEGF and Ang-1, Ang-1 pro
moted the adhesion of sorted primary Lin(-)TIE-2(+) cells to fibronectin, a
nd this adhesion enhanced proliferation of hematopoietic progenitor cells s
ynergistically with stem cell factor (SCF). Our findings suggest that TIE-2
/angiopoietins may act as critical regulators of proliferation of hematopoi
etic progenitors and endothelial cells in a synergistic manner. (C) 1999 Ac
ademic Press.