Expression of DC-SIGN and DC-SIGNR on human sinusoidal endothelium: a role for capturing hepatitis C virus particles.
Hepatic sinusoidal endothelial cells are unique among endothelial cells in their ability to internalize and process a diverse range of antigens. DC-SIGNR, a type 2 C-type lectin expressed on liver sinusoids, has been shown to bind with high affinity to hepatitis C virus (HCV) E2 glycoprotein. DC-SIGN is a closely related homologue reported to be expressed only on dendritic cells and a subset of macrophages and has similar binding affinity to HCV E2 glycoprotein. These receptors function as adhesion and antigen presentation molecules. We report distinct patterns of DC-SIGNR and DC-SIGN expression in human liver tissue and show for the first time that both C-type lectins are expressed on sinusoidal endothelial cells. We confirmed that these receptors are functional by demonstrating their ability to bind HCV E2 glycoproteins. Although these lectins on primary sinusoidal cells support HCV E2 binding, they are unable to support HCV entry. These data support a model where DC-SIGN and DC-SIGNR on sinusoidal endothelium provide a mechanism for high affinity binding of circulating HCV within the liver sinusoids allowing subsequent transfer of the virus to underlying hepatocytes, in a manner analogous to DC-SIGN presentation of human immunodeficiency virus on dendritic cells.
Lai
Wai K
WK
Liver Research Laboratories, Institute of Biomedical Research, Birmingham University, Edgbaston, B15 2TH, United Kingdom. w.k.lai@bham.ac.uk
Sun
Phoebe J
PJ
Zhang
Jie
J
Jennings
Adam
A
Lalor
Patricia F
PF
Hubscher
Stefan
S
McKeating
Jane A
JA
Adams
David H
DH
D015815:Cell Adhesion Molecules / Q000096:biosynthesis*; D042783:Endothelial Cells / Q000378:metabolism*; D004727:Endothelium / Q000378:metabolism; D005434:Flow Cytometry; D016174:Hepacivirus / Q000472:pathogenicity; D006801:Humans; D007150:Immunohistochemistry; D015847:Interleukin-4 / Q000378:metabolism; D037181:Lectins, C-Type / Q000096:biosynthesis*; D008099:Liver / Q000378:metabolism*; D011956:Receptors, Cell Surface / Q000096:biosynthesis*; D014759:Viral Envelope Proteins / Q000378:metabolism*; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin
D015815:Cell Adhesion Molecules; D015847:Interleukin-4; D037181:Lectins, C-Type; D011956:Receptors, Cell Surface; D014759:Viral Envelope Proteins; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin; C433029:CLEC4M protein, human; C091015:glycoprotein E2, Hepatitis C virus