Involvement of up-regulated CXC chemokine ligand 16/scavenger receptor that binds phosphatidylserine and oxidized lipoprotein in endotoxin-induced lethal liver injury via regulation of T-cell recruitment and adhesion.
A murine model of endotoxin-induced lethal liver injury induced by Mycobacterium bovis BCG plus lipopolysaccharide (LPS) has been widely accepted and used. It has been reported that T cells play an important role in the pathogenesis of liver damage in this model. However, the precise mechanisms involved in regulation of the trafficking of effector T cells need to be elucidated. In the present study, we first reported that CXCL16/SR-PSOX (CXC chemokine ligand 16/scavenger receptor that binds phosphatidylserine and oxidized lipoprotein), a chemokine containing both membrane-anchored and soluble forms, was strongly up-regulated and predominantly distributed in the vascular endothelium in the injured liver tissue in the model. The secretory and membrane-anchored CXCL16/SR-PSOX functioned as a chemokine and an adhesive molecule, respectively, to attract T cells to a tumor necrosis factor alpha-activated endothelial cell line (SVEC) in vitro. To further identify the pathophysiological roles of CXCL16/SR-PSOX in the liver injury, the anti-CXCL16 antibody was administered to the BCG-primed mice before LPS challenge in vivo. Significant protection effects were observed with 70% of mice regarding lethality, the massive necrosis in the liver was reduced, and the intrahepatic infiltrating T cells were significantly inhibited. Taken together, these findings strongly suggest that functional CXCL16/SR-PSOX, as both a chemokine and an adhesion molecule, may be involved in the pathogenesis of the endotoxin-induced lethal liver injury via recruitment and adhesion of activated T cells to the vascular endothelium.
Department of Immunology and Key Laboratory of Molecular Medicine of Ministry of Education, Shanghai Medical College of Fudan University, 138 Yi Xue Yuan Road, Shanghai 200032, People's Republic of China.
Huanbin
H
Xu
Wei
W
Xu
Yiwei
Y
Chu
Yanping
Y
Gong
Zhenggang
Z
Jiang
Sidong
S
Xiong
D000818:Animals; D002448:Cell Adhesion; D002465:Cell Movement; D000075743:Chemokine CXCL16; D054427:Chemokine CXCL6; D019743:Chemokines, CXC / Q000502:physiology*; D004731:Endotoxins / Q000633:toxicity*; D008074:Lipoproteins / Q000378:metabolism; D008099:Liver / Q000187:drug effects*; D008297:Male; D008565:Membrane Proteins / Q000502:physiology*; D051379:Mice; D008807:Mice, Inbred BALB C; D010084:Oxidation-Reduction; D010718:Phosphatidylserines / Q000378:metabolism; D011971:Receptors, Immunologic / Q000502:physiology*; D051116:Receptors, Scavenger; D013601:T-Lymphocytes / Q000502:physiology*; D015854:Up-Regulation
D000075743:Chemokine CXCL16; D054427:Chemokine CXCL6; D019743:Chemokines, CXC; C498926:Cxcl16 protein, mouse; D004731:Endotoxins; D008074:Lipoproteins; D008565:Membrane Proteins; D010718:Phosphatidylserines; D011971:Receptors, Immunologic; D051116:Receptors, Scavenger