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.
MediCity Research Laboratory, Turku University, Tykistökatu 6A, 20520 Turku, Finland. marko.salmi@utu.fi
Marko
M
Salmi
Kaisa
K
Koskinen
Tiina
T
Henttinen
Kati
K
Elima
Sirpa
S
Jalkanen
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