Hematopoietic activity of tek-ligand, angiopoietins in murine bone marrow cells

TEK is a receptor tyrosine kinase specific to vascular endothelial cells and hematopoietic cells. It plays critical roles in vascular maturation, integrity and remodeling, and also in the development of definitive hematopoiesis in AGM region. To characterize TEK function in the bone marrow hematopoiesis, we examined the effect of two recently identified TEK-ligands, Angiopoietin-1 and -2 (which were provided by Dr. Yancopoulos, NY). Angiopoietin-1, as a physiologically predominant ligand, effectively induced phosphrylation of TEK and adhesion of TEK+ cells to fibronectin and the adhesive effect was blocked by ROD peptide. Angiopoietins supported the proliferation of hematopoietic cells in the culture of total marrow cells, and this effect was blocked by TEK-Fc fusion protein or ROD. Angiopoietins alone did not affect the proliferation of PECAM-1 ⁺ endothelial cells, but by the addition of VEGF, vascular network formation was synergistically enhanced. Angiopoietin-1 stimulated the proliferation of sorted TEK⁺ cells in the presence of SCF and IL-6. TEK-Fc was intraperitoneally injected into murine neonates. tissue sections and flow cytometric analysis revealed that hematopoietic progenitors including Lin"Kit⁺ cells significantly reduced. Our findings suggest that TEK signaling is essential to the adherence and proliferation of hematopoietic cells.