CLEVER-1 mediates lymphocyte transmigration through vascular and lymphatic endothelium.
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.
Salmi
Marko
M
MediCity Research Laboratory, Turku University, Tykistökatu 6A, 20520 Turku, Finland. marko.salmi@utu.fi
Koskinen
Kaisa
K
Henttinen
Tiina
T
Elima
Kati
K
Jalkanen
Sirpa
S
D002196:Capillaries / Q000502:physiology; D002448:Cell Adhesion; D015816:Cell Adhesion Molecules, Neuronal; D002465:Cell Movement / Q000502:physiology; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000502:physiology; D004730:Endothelium, Vascular / Q000502:physiology*; D006801:Humans; D007249:Inflammation; D036904:Leukocyte Rolling / Q000502:physiology*; D007963:Leukocytes, Mononuclear / Q000502:physiology; D008208:Lymphatic System / Q000502:physiology*; D008214:Lymphocytes / Q000502:physiology*; D018919:Neovascularization, Physiologic / Q000502:physiology; D016201:Receptors, Lymphocyte Homing; D012879:Skin Physiological Phenomena; D014471:Umbilical Veins
D015816:Cell Adhesion Molecules, Neuronal; D016201:Receptors, Lymphocyte Homing; C449926:STAB1 protein, human