Studies on the Dynamics of Biogenic Amines in Inflammatory Reactions

组胺是由组氨酸脱羧酶(HDC)形成的。鸟氨酸脱羧酶(ODC)是多胺合成的限速酶。在此资助期限之前，作者澄清了以下几点：(1)小鼠体内注射几种炎性物质后，肝、肺、脾和骨髓等组织的HDC和ODC活性在3~5h内达到高峰。在肝脏中，5-羟色胺也会积累。(2)巨噬细胞可能参与这些反应的诱导。(3)巨噬细胞系P388Dl细胞可产生诱导上述反应的因子。这些因子的分子量和等电点与重要的免疫调节因子白细胞介素1(IL-1)的分子量和等电点相同。(4)药理研究表明，肝脏中5-羟色胺的蓄积可能是引起低血糖和肝炎的原因之一。在助学金期间，澄清了以下内容：(5)白介素1、肿瘤坏死因子、…巨噬细胞的更多产物，刺激或抑制某些类型的肿瘤细胞的生长。这些效应与细胞中ODC活性的表达或抑制有关。(6)与炎症介质一样，重组人IL-1和肿瘤坏死因子也可诱导所有的反应。此外，IL-1和肿瘤坏死因子的结合增强了这些反应。这些结果证实了(3)中的观察结果，并表明IL-1和/或TNF可能是这些反应的调节因子。(7)5-羟色胺在肝脏中的蓄积是由于其他部位5-羟色胺的修饰所致。结论：上述生物胺的动力学机制与炎症或免疫反应的调节密切相关。该项目目前和未来的成果将为理解免疫反应的炎症提供新的线索。关于(6)的两篇论文中有一篇正在出版，另一篇正在准备中。为了发表(7)，还需要进一步的实验。(5)的研究是与美国国家癌症研究所(马里兰州弗雷德里克)合作进行的。较少

Histamine is formed by histidine decarboxylase (HDC). Ornithine decarboxylase (ODC) is a rate-limiting enzyme in polyamine synthesis. The author had clarified the followings before the term of this grant-in-aid: (1) The injections of some kinds of inflammatory agents into mice induce HDC and ODC activities reaching peaks within 3 to 5 h in the tissues such as liver, lung, spleen and bone marrow. In the liver, serotonin is also accumulated. (2) Macrophages may participate in the induction of these responses. (3) P388Dl cells, a macrophage cell line, produce the factors capable of inducing all these responses. The molecular weight and isoelectric points of the factors are identical with those of interleukin-1 (IL-1), an important immuno-regulator. (4) Pharmacological suties suggest that the accumulation of 5HT in the liver may become a cause producing hypoglycaemia and hepatitis.During the term of the grant-in-aid, the followings were clarified: (5) IL-1 and TNF (tumor necrosis factor), … More products of macrophages, stimulate or suppress the growth of some types of tumor cells. These effects correlate to the expression or suppression of ODC activity in the cells. (6) Recombinant human IL-1 and TNF also induce all the responses as the inflammatory agents did. In addition, the combination of IL-1 and TNF enhanced these responses. These results confirms the observations in (3) and indicate that IL-1 and/or TNF can be regulators of these responses. (7) The accumulation of 5ht in the liver is due to the modilization of 5HT from other sites. Platelets may be involved in this mechanism.Conclusion: The mechainisms of the dynamics of the biogenic amines described above intimately correlate to the regulation of inflammatory or immune responses. The present and fufure fruits of this project will provide new clues for understanding inflammation of immune responses.One of two papers concerning (6) is in press and the other is in preparation. Further experiments are necessary for the publication of (7). The research on (5) was collaborated with National Cancer Institute of USA (Frederick, MD). Less