Human soluble E‐selectin immunoadhesin inhibits leukemic monocyte adhesion to endothelial cells

Abstract

Immunoadhesins are immunoglobulin (Ig)-like chimeric proteins comprised of target-binding regions fused to the Fc-hinge region of Ig, and are designed to have a long half-life and antibody-like properties. In an effort to find a good candidate for therapeutic use for inflammatory responses, we constructed a soluble human E-selectin immunoadhesin containing the extracellular region of human E-selectin fused to the Fc-hinge region of human IgG, and determined its effects on leukocyte adhesion and rolling in vitro. Our results revealed that the adhesion of leukocytes to endothelial cells was efficiently inhibited in the presence of 50 nM E-selectin immunoadhesin. In addition, the E-selectin immunoadhesin significantly inhibited leukocyte rolling on endothelial cells in perfusion experiments performed at 1.0 dyne/cm(2) wall shear stress. These findings indicate that our E-selectin immunoadhesin decreases leukocyte attachment and rolling in vitro, suggesting that this immunoadhesin may be a promising candidate for therapeutic anti-inflammatory use.