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Blood, 15 December 2004, Vol. 104, No. 13, pp. 3849-3857.
Prepublished online as a Blood First Edition Paper on August 5, 2004; DOI 10.1182/blood-2004-01-0222.
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Submitted January 20, 2004
Accepted June 25, 2004
CLEVER-1 mediates lymphocyte transmigration through vascular and lymphatic endothelium
Marko Salmi*, Kaisa Koskinen, Tiina Henttinen, Kati Elima, and Sirpa Jalkanen
MediCity Research Laboratory, Turku University, Turku, Finland; National Public Health Institute, Turku, Finland
* Corresponding author; email: marko.salmi{at}utu.fi.
Common lymphatic endothelial and vascular endothelial receptor-1 (CLEVER-1; also known as stabilin-1 or FEEL-1) is a large multifunctional glycoprotein implicated in scavenging, angiogenesis and cell adhesion. Here we studied the function of human CLEVER-1 in leukocyte trafficking. Lymphatic vessels expressed CLEVER-1 constitutively in skin in vivo, whereas on vascular endothelium it only appeared upon inflammation. On isolated vascular endothelial cells, CLEVER-1 supported rolling and transmigration of peripheral blood mononuclear cells (PBMC) under physiologically relevant laminar shear stress. Intriguingly, CLEVER-1 also mediated transmigration of leukocytes through cultured lymphatic endothelium under static conditions. Thus, synthesis of CLEVER-1 is differentially regulated on the two anatomically distinct vascular beds and it mediates the transmigration step of the leukocyte traffic in both of them. Notably, CLEVER-1 is the first adhesion molecule shown to be involved in the PBMC transmigration through the lymphatic arm of the immune system.
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