A novel model of acute liver injury in mice induced by T cell-mediated immune response to lactosylated bovine serum albumin.
The present study aimed to establish a murine liver injury model with T cell-mediated immune response to mimic the cellular immunological pathogenesis of hepatitis. Bovine serum albumin was conjugated with lactose by redox to prepare lactosylated bovine serum albumin (LacBSA). The liver injury was induced in C57BL/6 mice by a T cell-mediated immune response to LacBSA. After a systemic injection of LacBSA, which elicited immune response in mice sensitized twice with LacBSA, liver injury was observed with obvious increase of aminotransferase levels in serum and hepatocelluar damage in liver histology. However, the splenectomy before the elicitation significantly alleviated the liver injury. Direct contact between spleen T cells/nonparenchymal cells and hepatocytes was proved to be essential to induce the release of alanine aminotransferase in the culture supernatant. In addition, both levels of Fas mRNA in liver tissues and Fas Ligand in spleen cells were up-regulated at 6 h after the elicitation. The Fas mRNA expression was maintained in a relatively high level at 18 h while Fas Ligand began to decrease after 12 h. These results demonstrated that the T cell immune response to LacBSA could be successfully localized in the liver to induce an immunological liver injury in mice. The pathogenesis of the liver injury might involve the interaction between the liver-infiltrating lymphocytes and hepatocytes through Fas/FasL pathway.
State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing, China.
Ling
L
Xu
Ying
Y
Zhao
Yu
Y
Qin
Qiang
Q
Xu
D000208:Acute Disease; D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D001219:Aspartate Aminotransferases / Q000097:blood; D004195:Disease Models, Animal; D053222:Fas Ligand Protein; D008024:Ligands; D008099:Liver / Q000276:immunology / Q000293:injuries* / Q000473:pathology; D008297:Male; D008562:Membrane Glycoproteins / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008813:Mice, Inbred ICR; D012333:RNA, Messenger / Q000032:analysis; D018124:Receptors, Tumor Necrosis Factor / Q000276:immunology; D012709:Serum Albumin / Q000276:immunology*; D013154:Spleen / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*; D000637:Transaminases / Q000097:blood; D048069:Tumor Necrosis Factors / Q000276:immunology; D015854:Up-Regulation / Q000276:immunology; D019014:fas Receptor
D053222:Fas Ligand Protein; C491899:Fas protein, mouse; C505658:Fasl protein, mouse; D008024:Ligands; D008562:Membrane Glycoproteins; D012333:RNA, Messenger; D018124:Receptors, Tumor Necrosis Factor; D012709:Serum Albumin; D048069:Tumor Necrosis Factors; D019014:fas Receptor; C049720:lactosylated serum albumin; D000637:Transaminases; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase