Study on the role of lymphocytes on organ failure and disturbed host defense mechanism due to infection and stress

淋巴细胞在感染和应激引起的器官衰竭和宿主防御机制紊乱中的作用研究

• 批准号: 09470324
• 负责人: INABA Hideo
• 金额: $ 4.8万
• 依托单位: AKITA UNIVERSITY
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 1997
• 资助国家: 日本
• 起止时间: 1997 至 1999
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-09470324/
• 关键词: lymphocyte; apoptosis; hydrogen peroxide; hepatocytes; endothelial cells; heat shock protein; bcl-2; ischemia; 低酸素; アポトーシス; 摘出潅流肝; OK-432; concanavalin A

Lympocytes may induce acute injuries of the perfused liver when sinusoidal endothelial cell apoptosis is induced by the administration of OK432 or ischemic challenge, and when lymphocytes are activated by concanavalin A. In the schemic liver, hydrogen peroxide derived from hepatocytes induces sisusoidal endothelial cell apoptosis in the midzone of Liver acinus as well as Hsp 72 expression in sinusoidal endothelial cells. An anti-apoptotic protein Bcl-2 is located in the inner membrane and crista of mitochondria in the hepatocytes. Localization of Bcl-2 is unchanged by the ischemic challenge.In a mouse model of severe infection and sepsis induced consequent administrations of Ok432 and lipopolysaccharide, both natural killer and lymphokine-activated killer activities are elevated, but lymphocytes are very sensitive to Fas-mediated apoptosis.

当OK432或缺血刺激诱导肝窦内皮细胞凋亡时，淋巴细胞可引起灌流肝脏的急性损伤，而刀豆蛋白A激活淋巴细胞时，肝细胞产生的过氧化氢诱导肝腺泡中区肝窦内皮细胞凋亡，并诱导肝窦内皮细胞表达HSP72。抗凋亡蛋白Bcl2定位于肝细胞线粒体的内膜和嵴。在严重感染和脓毒症的小鼠模型中，应用Ok432和脂多糖后，自然杀伤细胞和淋巴因子激活的杀伤细胞活性都升高，但淋巴细胞对Fas介导的凋亡非常敏感。

项目成果

Motoyama S.Inaba H.: "Mitochondrial Ubiquinone (coenzymeQ10) : Biochemical functional, medical and therapeutic aspect in human health"Academic Press (in press). (2000)

Motoyama S.Inaba H.：“线粒体泛醌（辅酶Q10）：人类健康中的生化功能、医学和治疗方面”学术出版社（正在出版）。

Motoyama S, Inaba H. et al.: "Bcl-2 is located predominantly in the inner membrane and crista of mitochondria in rat liver."Biochem Biophys Res Commun. 249. 628-636 (1998)

Motoyama S、Inaba H. 等人：“Bcl-2 主要位于大鼠肝脏线粒体的内膜和嵴中。”Biochem Biophys Res Commun。

Motoyama S, Inaba H, et al.: "Hydrogen peroxide derived from hepatocytes induces sinusoidal endothelial cell apoptosis in perfused hypoxic rat liver."Gastroenterology. 114. 153-163 (1998)

Motoyama S、Inaba H 等人：“源自肝细胞的过氧化氢在灌注缺氧的大鼠肝脏中诱导肝窦内皮细胞凋亡。”胃肠病学。

Motoyama S, Inaba H 他: "Biochemical,functional,medical and therapeutic aspect in human health and disease"Bcl-2 is located predominantly in the inner membrane and crista of mitochondria (In press). (2000)

Motoyama S、Inaba H 等人：“人类健康和疾病的生物化学、功能、医学和治疗方面”Bcl-2 主要位于线粒体的内膜和嵴（正在出版）（2000 年）。

Motoyama S ほか: "Hydrogen peroxide derived from nepatocytes induces sinusoidal endothelial cell apoptosis in perfused hypoxic rat liver" Gastroenterology. 114巻. 153-163 (1998)

Motoyama S 等人：“来自肾细胞的过氧化氢诱导灌注缺氧大鼠肝脏中的窦内皮细胞凋亡”胃肠病学。 114. 153-163 (1998)。