Studies on the mechanisms of liver cell injury in type A hepatitis

甲型肝炎肝细胞损伤的确切机制尚不清楚，宿主对病毒感染的反应，包括免疫机制，被认为参与了甲型肝炎肝细胞损伤的发病机制。为了阐明其机制，我们用食蟹猴肾细胞JTC-12-P_3感染培养细胞系，进行了电镜观察。本研究证实，尽管HAV在JTC-12-P_3细胞中增殖，但未观察到细胞病变效应。用~（13）Cr标记感染和未感染的JTC-12-P_3细胞，然后用~（13<51>）Cr标记的细胞与正常人甲型肝炎患者和正常食蟹猴的淋巴细胞孵<51>育，观察NK细胞和LAK细胞活性在甲型肝炎发病中的作用。用<51>人淋巴细胞作对照，<51>感染与未感染的JTC-12-P_3细胞，即使用甲型肝炎患者淋巴细胞作对照，其~（13）Cr的释放量也无显著性差异。而用食蟹猴淋巴细胞感染时，细胞损伤明显增加，说明NK或LAK细胞活性至少在一定程度上参与了甲型肝炎的肝细胞损伤，这种非特异性的宿主反应在自体或异体关系中似乎是有效的。

Precise mechanisms of liver cell injury in type A hepatitis are not yet clear and host responses to viral infection including immune mechanisms were thought to be involved in the pathogenesis of liver cell damage in Hepatitis A.To clarify the mechanisms, the electron microscopic observation of HAV infected cultured cell line was performed using JTC-12-P_3 cells derived from cynomolgus monkey kidney. Through this study, it was confirmed that cytopathic effect was not observed despite the propagation of HAV in JTC-12-P_3 cells. Furthermore crystalline array of HAV was observed in the cytoplasm which was not yet reported ever in HAV propagation.Next, the role of NK or LAK cell activity in type A hepatitis was investigated.Infected and non infected JTC-12-P_3 cell were labeled with ^<51>Cr, and then lymphocytes, treated and not treated with IL-2, from normal humans type A hepatitis patients and normal cynomolgus monkeys were incubated with these ^<51>Cr labeled cells. The release of ^<51>Cr in supernatant was assayed and the degree of cell damage was estimated.When human lymphocytes were used, no significant difference of ^<51>Cr release was observed between infected and non infected JTC-12-P_3 cells even in the use of type A hepatitis patients lymphocytes. While, when cynomolgus monkey lymphocytes were used, significant increase of cell damage was observed in infected cultures.Thus NK or LAK cell activity seemed to be involved, at least in some extent, in the liver cell damage of type A hepatitis, and this kind of non specific host response appeared to be effective in autologous or allogeneic relationships.