Involvement of natural killer cells in PolyI:C-induced liver injury.
OBJECTIVE
The roles of T cells, natural killer T cells (NKT) and macrophages in autoimmune hepatitis have been well documented. However, the roles of natural killer (NK) cells in liver injury remain obscure. Here we examined the effect of Polyinosinic: polycytidylic acid (PolyI:C)-activated NK cells on liver injury.


METHODS
Mice were intraperitoneally injected with PolyI:C at a dose of 20mug/g body wt. The percentage and absolute number of NK cells in the liver were analyzed with flow cytometry. Serum alanine transaminase (ALT) and aspartate aminotransferase (AST) assay and H-E staining were used to evaluate the liver injury.


RESULTS
Following PolyI:C injection, NK cells accumulation and activation occurred in the liver. Meanwhile, slight elevation of ALT/AST in the serum, mild inflammation and focal necrosis in the liver were also observed. Depletion of NK cells markedly attenuated PolyI:C-induced liver injury. Neutralization of endogenous Interleukin-12 produced by Kupffer cells abrogated the accumulation of NK cells in the liver and subsequent liver injury. The liver injury was also alleviated by neutralization of vascular cell adhesive molecule-1.


CONCLUSIONS
These findings suggest that PolyI:C preferentially recruits and activates hepatic NK cells, which may be responsible for the mild hepatitis.
Dong
Zhongjun
Z
School of Life Sciences, University of Science and Technology of China, 443 Huangshan Road, Hefei, Anhui 230027, China.
Wei
Haiming
H
Sun
Rui
R
Hu
Zhiqing
Z
Gao
Bin
B
Tian
Zhigang
Z
D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D001219:Aspartate Aminotransferases / Q000097:blood; D056486:Chemical and Drug Induced Liver Injury / Q000209:etiology* / Q000473:pathology; D007274:Injections, Intraperitoneal; D007371:Interferon-gamma / Q000378:metabolism; D018664:Interleukin-12 / Q000378:metabolism; D007694:Killer Cells, Natural / Q000187:drug effects / Q000473:pathology; D007728:Kupffer Cells / Q000378:metabolism; D008099:Liver / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008213:Lymphocyte Activation; D051379:Mice; D008807:Mice, Inbred BALB C; D009336:Necrosis; D011066:Poly C / Q000008:administration & dosage / Q000494:pharmacology; D019010:Vascular Cell Adhesion Molecule-1 / Q000378:metabolism
D019010:Vascular Cell Adhesion Molecule-1; D018664:Interleukin-12; D011066:Poly C; D007371:Interferon-gamma; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase