Studies on the regulatory systems and its physiological significances of the hepatic induction of acute-phase reactants.

(1)肝脏急性期反应物生成的抑制和刺激系统的研究。通过与活化的巨噬细胞或胸腺细胞共培养，刺激培养的大鼠肝细胞产生t -激肽原，这是一种典型的大鼠急性期反应物。负责刺激肝脏T-激肽原产生的因子被确定为来自活化巨噬细胞的白细胞介素-6和干扰素- α，以及来自活化胸腺细胞的白细胞介素-6。肝脏t -激肽原的产生受到来自脾细胞的一种因子的抑制，而脾细胞此前已被脂多糖长期激活。巨噬细胞被认为是释放一种抑制因子的细胞，而这种抑制性巨噬细胞的诱导过程需要T细胞(2)。急性期反应物激肽原对肿瘤生长的抑制活性。小鼠低分子激肽原、大鼠t激肽原和蛋清胱抑素对肿瘤细胞的体外抑制作用更明显。我们得到的证据表明，这种活性是由于激肽原或胱抑素抑制了组织蛋白酶- l样蛋白酶。在细胞周期的G0/ g1期和s期，激肽原对肿瘤细胞的生长有抑制作用(3)。血管紧张素原作为急性期反应物。炎症诱导大鼠血浆血管紧张素原水平升高。通过对大鼠肝癌细胞的体外实验，确定了引起急性期反应的因子是白细胞介素-6。炎症诱导的血浆血管紧张素原升高引起血浆肾素活性增加，表明炎症条件下体内血管紧张素I的形成增强。与t -激肽原或α _2-巨球蛋白相比，即使在慢性炎症的情况下，血浆血管紧张素原的升高也是短暂的，这表明血管紧张素原产生的调节系统可能不同于其他急性期反应物。少

(1). Studies on the suppressive and the stimulatory systems in the hepatic production of acute-phase reactant.Production of T-kininogen, a typical acute-phase reactant in the rat, in cultured rat hepatocytes was stimulated by the coculture with activated macrophages or thymocytes. The factors responsible for stimulating hepatic T- kininogen production were identified to be interleukin-6 and interferon-alpha as factors derived from activated macrophages, and interleukin-6 from activated thymocytes. Hepatic T-kininogen production was inhibited by a factor derived from splenic cells, which had previously been activated for a long time by lipopolysaccharide. Macrophages were identified to be cells releasing a suppressive factor, and T cells were required for the induction process of such suppressive macrophages.(2). Inhibitory activity of kininogens an acute-phase reactant on tumor growth.Mouse low-molecular-weight kininogen, as well as rat T-kininogen and egg white cystatin, had the abili … More ty to inhibit the growth of tumor cells in vitro. we obtained evidence that the activity was due to inhibition of cathepsin-L- like proteinase by kininogens or cystatin. Kininogens inhibited the growth of tumor cells between G0/G1-phase-and S-phase of cell cycle.(3). Angiotensinogen as an acute-phase reactant.Angiotensinogen level in plasma was increased in the rat by the induction of inflammation. The factor responsible for the acute-phase response was identified to be interleukin-6 by an in vitro experiment using rat hepatoma cells. Inflammation-induced elevation of plasma angiotensinogen caused an increase in plasma renin-activity, suggesting that angiotensin I formation in vivo is enhanced in the inflammatory conditions. In contrast with T-kininogen or alpha_2-macroglobulin, elevation of plasma angiotensinogen was transient even in the condition of chronic inflammation, suggesting that a regulatory system of angiotensinogen production may be different from that of other acute-phase reactants. Less