Novel syngeneic liver hapten protein compounds play different roles in pathogenesis of autoimmune hepatitis in the C57BL/6 mouse

Autor: Chen, Wen-Ji, Wang, Jin-Hui, Wang, Shu-Bing, Zhi, Min, Chen, Jie, Li, Zhi-Xun, Li, Yu-Yuan, Nie, Yu-Qiang, Chen, Min-Hu
Rok vydání: 2013
Předmět:
Zdroj: Hepato-gastroenterology. 60(126)
ISSN: 0172-6390
Popis: The autoimmune hepatitis (AIH) model in C57BL/6 mice with syngeneic hapten S100 and adjuvant injected intraperitoneally has been designed to elucidate the pathogenesis of AIH. Three separate hapten peak proteins, peak I, peak II and peak III, could be derived from S100, but little is understood their roles on the development of AIH. This study aims to learn more about these roles on pathogenesis of AIH.Novel AIH C57BL/6 mouse models were developed by weekly immunization by intraperitoneal injection with syngeneic S100 liver proteins and the three separated hapten peak proteins emulsified covalently in complete Freund's adjuvant (CFA) for 4 weeks and sacrificed for liver histopathological study. Additionally, TNF-α and INF-γ in culture supernatants of spleen lymphocytes of healthy C57BL/6 mice cultured together with S100 plus CFA for 48 hours were detected, and the T-lymphocytes proliferative response after stimulation with crude S100, peak I, II or III proteins were also assessed.Data showed that hepatitis induced by CFA+S100 was accompanied with more severe inflammation characterized by diffusely distributed liver necrosis and enhanced lymphocyte infiltration in portal tracts, while hepatitis induced by peak I+CFA was characterized by mass lymphocyte infiltration, occasional isolated liver necrosis and many acidophilic bodies, which was more similar to autoimmune hepatitis; hepatitis induced by peak II+CFA was characterized by massive liver necrosis and mild lymphocyte infiltration; hepatitis induced by peak III+CFA was characterized by mild inflammation with isolated acidophilic bodies or dotted hepatocellular necrosis. TNF-α, INF-γ from culture supernatants were increased, and T-lymphocyte proliferative response stimulated with peak I protein significantly increased compared with those stimulated with crude S100, peak II or III proteins.Syngenic S100 liver protein and its three separated hapten proteins have different roles in the pathogenesis of AIH, and peak I protein may be important in its development.
Databáze: OpenAIRE