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Originally published online as doi:10.1189/jlb.0107052 on August 3, 2007

Published online before print August 3, 2007
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(Journal of Leukocyte Biology. 2007;82:1156-1165.)
© 2007 by Society for Leukocyte Biology

Stabilin-2 is involved in lymphocyte adhesion to the hepatic sinusoidal endothelium via the interaction with {alpha}Mβ2 integrin

Mi-Yeon Jung*,1, Seung-Yoon Park{dagger},1 and In-San Kim*,2

* Department of Biochemistry and Cell Biology, Cell and Matrix Research Institute, School of Medicine, Kyungpook National University, Daegu, Korea; and
{dagger} Department of Biochemistry, School of Medicine, Dongguk University, Kyungju, Korea

2 Correspondence: Department of Biochemistry and Cell Biology, Cell and Matrix Biology Research Institute, School of Medicine, Kyungpook National University, Daegu 700-422, Korea. E-mail: iskim{at}knu.ac.kr

Although lymphocyte recirculation to the endothelium plays a critical role in the movement of immune cells from the blood into tissues and sites of inflammation, the mechanisms involved in lymphocyte trafficking via the hepatic circulation have yet to be elucidated fully. In this study, we investigated the role of stabilin-2, which is expressed specifically in the sinusoidal endothelium, in the adhesion of lymphocytes to the hepatic endothelium. Stabilin-2-expressing cells mediate the adhesion of PBLs. This interaction was attributed specifically to the interaction of stabilin-2 with {alpha}Mβ2 integrin. Using mutant stabilin-2 molecules with deletions in the extracellular domain, we mapped the binding site for {alpha}Mβ2 integrin to the fasciclin 1 (FAS1) domains of stabilin-2. The specificity of the interaction between {alpha}Mβ2 integrin and the FAS1 domain was confirmed further by binding assays using neutralizing antibodies. More physiologically, we showed that the down-regulation of stabilin-2 results in the defective binding of lymphocytes to hepatic sinusoidal endothelial cells under conditions of static and physiological flow. Together, these data show that stabilin-2 can reconstitute the lymphocyte–endothelial adhesion cascade under physiological shear stress. We propose a critical role for stabilin-2 in lymphocyte adhesion to specialized endothelia, such as that of the hepatic sinusoid.

Key Words: FAS1 domain • molecules • FEEL-2 • HARE




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