Blood, Vol. 93 No. 11 (June 1), 1999:
pp. 3785-3791
Noninflammatory Expression of E-Selectin Is Regulated by Cell Growth
Jianying Luo,
Gretchen Paranya, and
Joyce Bischoff
From the Surgical Research Laboratory, Children's Hospital and the
Department of Surgery, Harvard Medical School, Boston, MA.
E-selectin, an endothelial-specific adhesion molecule best known for
its role in leukocyte adhesion, is not detected in quiescent endothelial cells, but is induced by inflammatory stimuli. However, E-selectin is also expressed in proliferating endothelial cells under
noninflammatory conditions in vivo and in vitro, suggesting that
E-selectin is also regulated by growth signals. To investigate E-selectin expression in lipopolysaccharide-stimulated versus nonstimulated proliferating cells, we analyzed the distribution of
E-selectin-positive human microvascular endothelial cells in G0/G1, S, and G2/M phases of the
cell cycle under both conditions. Lipopolysaccharide treatment resulted
in uniformly increased E-selectin expression in cells in
G0/G1, S, and G2/M. In contrast,
levels of E-selectin in nonstimulated proliferating cells showed a
linear correlation with the percentage of cells in G2/M.
E-selectin in proliferating endothelial cells was not reduced by
addition of soluble tumor necrosis factor-
-receptor or soluble
interleukin-1-receptor indicating that its expression was not due to
endogenous production of either cytokine. In addition, E-selectin was
increased in cells stimulated with basic fibroblast growth factor, a
well-known mitogen for endothelial cells. E-selectin in proliferating
endothelial cells is functional, as shown by E-selectin-dependent
adhesion of the promyelocytic leukemia cell line HL-60 to subconfluent human microvascular endothelial cells. In summary, these studies indicate that E-selectin can be regulated by a non-inflammatory pathway
that is related to the proliferative state of the endothelium.
