CLEVER-1 mediates lymphocyte transmigration through vascular and lymphatic endothelium

: Salmi M, Koskinen K, Henttinen T, Elima K, Jalkanen S

Publisher: AMER SOC HEMATOLOGY

: 2004

: Blood

: BLOOD

: 104

: 13

: 3849

: 3857

: 9

: 0006-4971

DOI: https://doi.org/10.1182/blood-2004-01-0222

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. (C) 2004 by The American Society of Hematology.

Biochemistry, cell and molecular biology