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

甲型肝炎肝细胞损伤机制研究

• 批准号: 62480193
• 负责人: SUZUKI Shiro
• 金额: $ 4.29万
• 依托单位: Mie University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (B)
• 财政年份: 1987
• 资助国家: 日本
• 起止时间: 1987 至 1989
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-62480193/
• 关键词: Type A Hepatitis; Liver cell damage; HAV; Electron microscopy; Crystalline array; NK cell activity; LAK cell activity; HAV; 肝細胞障害機序; インタ-フェロン; 同種PBMC; NK細胞; LAK細胞

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.

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，对HAV进行电镜观察使用来自食蟹猴肾的 JTC-12-P_3 细胞进行感染的培养细胞系。通过这项研究，证实尽管HAV在JTC-12-P_3细胞中增殖，但并未观察到细胞病变效应。此外，在细胞质中观察到HAV的晶体阵列，这在HAV传播中尚未报道。接下来，研究了NK或LAK细胞活性在甲型肝炎中的作用。感染和未感染的JTC-12-P_3细胞用将来自正常人类甲型肝炎患者和正常食蟹猴的经 51 Cr处理和未用IL-2处理的淋巴细胞与这些经 51 Cr标记的细胞一起温育。测定上清液中^<51>Cr的释放量并估计细胞损伤的程度。当使用人淋巴细胞时，感染和未感染的JTC-12-P_3细胞之间观察到^<51>Cr释放量没有显着差异。甚至在使用甲型肝炎患者的淋巴细胞。然而，当使用食蟹猴淋巴细胞时，在受感染的培养物中观察到细胞损伤显着增加。因此，NK或LAK细胞活性似乎至少在某种程度上参与了甲型肝炎的肝细胞损伤，并且这种非特异性宿主反应似乎在自体或同种异体关系中有效。

项目成果

鈴木司郎,渡辺省三,馬場優: "Annual Review 消化器1989 岡博 他 編 A型肝炎と非A非B型肝炎 PP.122ー127" 中外医学社, 330 (1989)

Shiro Suzuki、Shozo Watanabe、Yu Baba：“Annual Review Gastroenterology 1989，由 Hiroshi Oka 等人编辑。甲型肝炎和非甲型、非乙型肝炎 PP.122-127”Chugai Igakusha，330 (1989)

鈴木司郎: "A型肝炎ウィルスの培養細胞内増殖に関する研究" 厚生省肝炎研究連絡協議会昭和60年度研究報告. 92-94 (1987)

铃木四郎：“甲型肝炎病毒在培养细胞中增殖的研究”卫生福利部肝炎研究联络委员会1985年研究报告92-94（1987）。

SUZUKI.S: Hepatitis Virus Marker, Hepatitis A Virus. in Diagnosis of the Liver.CHUGAI IGAKUSHA, Tokyo., 485 (1987)

SUZUKI.S：肝炎病毒标记，甲型肝炎病毒。

鈴木司郎: "Annual Review消化器 1989 岡博ほか編 A型肝炎の非A非B型肝炎 pp.122-127" 中外医学社, 330 (1989)

Shiro Suzuki：“胃肠病学年度评论 1989 年由 Hiroshi Oka 等人编辑。甲型肝炎到非甲非乙型肝炎第 122-127 页”中外医学社，330 (1989)

SUZUKI.S: Type A Hepatitis. in Studies of the Liver.DOHBUN SHOIN, Tokyo., 1314 (1987)

SUZUKI.S：甲型肝炎。