PARASITE INDUCED CATABOLISM IN MAMMALS

哺乳动物的寄生和细菌入侵与许多 常见的宿主代谢紊乱。其中之一就是归纳法 一种分解代谢状态，当时间延长时，可能会导致恶病质、休克和 死亡。我们最近分离出了一种巨噬细胞产物，cachectin，它是 是对布氏锥虫、伯氏杆菌和内毒素的反应，内毒素抑制 体内脂肪细胞脂蛋白脂酶和3T3-L1的合成 体外培养前脂肪细胞。 随后对cachectin对3T3-L1细胞的影响进行了分析 揭示了cachectin还能抑制其他关键合成代谢物质的合成。 合成脂肪酸所必需的酶-乙酰辅酶A羧基酶和 脂肪酸合成酶。对这些合成代谢酶的抑制作用很强。 选择性，因为用S35-蛋氨酸加标记细胞显示 放射性结合到蛋白质中的一般模式是 无论有没有调解人，情况都一样。Cachetin似乎是一个 免疫系统与身体其他细胞之间的通讯系统 参与能源储存和利用。 在当前的应用中，建议检查1)cachectin 可能处于恶病质状态，通常在感染的动物中观察到 对于寄生虫，2)cachectin对其他细胞的可能生物效应 类型；3)重组DNA技术克隆恶病质。 这些研究提供了阐明一种致病因素的可能性。 在各种寄生虫病中常见的方式，这可能导致 融合治疗方法的发展。

Parasitic and bacterial invasion of mammals is associated with a number of common metabolic derangements of the host. One of these is the induction of a catabolic state which, when prolonged, can lead to cachexia, shock and death. We have recently isolated a macrophage product, cachectin, which is made in response to T. brucei, P. berghei, and endotoxin that inhibits the synthesis of the enzyme lipoprotein lipase of adipocytes in vivo and 3T3-L1 pre-adipocytes in vitro. Subsequent analysis of the effect of the cachectin on the 3T3-L1 cells has revealed that cachectin also inhibits the synthesis of other key anabolic enzymes essential for fatty acid synthesis-acetyl Co-A carboxylase and fatty acid synthetase. The inhibition of these anabolic enzymes is highly selective, since plus labeling of the cells with S35-methionine reveals that the general pattern of incorporation of radioactivity into protein is the same with or without the mediator. Cachetin appears to be part of a communication system between the immune system and other cells of the body involved in energy storage and utilization. In the current application it is proposed to examine 1) what role cachectin might have in the cachectic state commonly observed in animals infected with parasites, 2) possible biological effects of cachectin on other cell types and 3) the cloning of cachectin by recombinant DNA technology. These studies offer the possibility of elucidating a type of pathogenic modality common in a wide variety of parasitic diseases, which may lead to the development of convergent therapeutic approaches.