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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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PLENARY PAPERS

CLEVER-1 mediates lymphocyte transmigration through vascular and lymphatic endothelium

Marko Salmi, Kaisa Koskinen, Tiina Henttinen, Kati Elima, and Sirpa Jalkanen

From the MediCity Research Laboratory and Department of Medical Microbiology, Turku University, Turku, Finland; and the National Public Health Institute, Turku, Finland.

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 appeared only upon inflammation. On isolated vascular endothelial cells, CLEVER-1 supported rolling and transmigration of peripheral blood mononuclear cells (PBMCs) 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 2 anatomically distinct vascular beds, and CLEVER-1 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. (Blood. 2004;104:3849-3857)


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Related Article in Blood Online:

A CLEVER molecule that regulates lymphoctye trafficking
Edward M. Conway and Peter Carmeliet
Blood 2004 104: 3840-3841. [Full Text] [PDF]



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