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Blood, 15 August 2001, Vol. 98, No. 4, pp. 1028-1037
HEMOSTASIS, THROMBOSIS, AND VASCULAR BIOLOGY
Stromal cells expressing ephrin-B2 promote the growth and
sprouting of ephrin-B2+ endothelial cells
Xiu-Qin Zhang,
Nobuyuki Takakura,
Yuichi Oike,
Tomohisa Inada,
Nicholas W. Gale,
George D. Yancopoulos, and
Toshio Suda
From the Department of Cell Differentiation, Institute
of Molecular Embryology and Genetics, Kumamoto University, Japan; and
Regeneron Pharmaceuticals, Tarrytown, NY.
Ephrin-B2 is a transmembrane ligand that is specifically expressed
on arterial endothelial cells (ECs) and surrounding cells and interacts
with multiple 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 boundaries. However, the
molecular mechanism during vasculogenesis and angiogenesis remains
unclear. Manipulative functional studies were performed on these
proteins in an endothelial cell system. Using in vitro stromal cells
(OP9 cells) and a paraaortic splanchnopleura (P-Sp) coculture system,
these studies found that the stromal cells expressing ephrin-B2
promoted vascular network formation and ephrin-B2+ EC
proliferation and that they also induced the recruitment and proliferation of -smooth muscle actin ( -SMA)-positive
cells. Stromal cells expressing EphB4 inhibited vascular network
formation, ephrin-B2+ EC proliferation, and
-SMA+ cell recruitment and proliferation. Thus, these
data suggest that ephrin-B2 and EphB4 mediate reciprocal interactions
between arterial and venous ECs and surrounding cells to form each
characteristic vessel.

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