Stromal cells expressing ephrin-B2 promote the growth and sprouting of ephrin-B2(+) endothelial cells

Ephrin-B2 is a transmembrane ligand that is specifically expressed on arter ial endothelial cells (ECs) and surrounding cells and interacts with multip le EphB class receptors. Conversely, EphB4, a specific receptor for ephrin- B2, is expressed on venous ECs, and both ephrin-B2 and EphB4 play essential roles in vascular development. The bidirectional signals between EphB4 and ephrin-B2 are thought to be specific for the interaction between arteries and veins and to regulate cell mixing and the making of particular boundari es. However, the molecular mechanism during vasculogenesis and angiogenesis remains unclear. Manipulative functional studies were performed on these p roteins in an endothelial cell system. Using in vitro stromal cells (OP9 ce lls) and a paraaortic splanchnopleura (P-Sp) coculture system, these studie s found that the stromal cells expressing ephrin-B2 promoted vascular netwo rk formation and ephrin-B2(+) EC proliferation and that they also induced t he recruitment and proliferation of alpha -smooth muscle actin (alpha -SMA) -positive cells. Stromal cells expressing EphB4 inhibited vascular network formation, ephrin-B2+ EC proliferation, and alpha -SMA(+) cell recruitment and proliferation. Thus, these data suggest that ephrin-B2 and EphB4 mediat e reciprocal interactions between arterial and venous ECs and surrounding c ells to form each characteristic vessel. (C) 2001 by The American Society o f Hematology.