PARASITE INDUCED CATABOLISM IN MAMMALS

哺乳动物的寄生和细菌入侵与 宿主常见代谢紊乱的数量。这其中的一个 是一种分解代谢状态的诱导，当时间延长时，可以 导致恶病质、休克和死亡。巨噬细胞的产物， Cachextia，这是对布氏毛滴虫的回应。P.berghei。 和内毒素，抑制酶的合成 体内脂肪细胞和3T3-L1前脂肪细胞的脂蛋白脂酶 在试管中。最近被隔离了。 小鼠恶病质的微测序和随后的克隆 该恶病质与肿瘤坏死因子(肿瘤坏死因子)相同。 在过去的几年里，一些生物活动 与cachectin有关的物质已被鉴定出来。这些都有 包括有选择地关闭转录的能力 特定的合成代谢基因，促进厌食、体重减轻和贫血， 引起发热、出血性坏死、肾小管坏死和致死 令人震惊。抗恶病质/肿瘤坏死因子抗体可预防 老鼠对内毒素和狒狒对致死性败血症。它就是这样 似乎寄主对入侵反应过度，并产生大量的毒物 可可菌素/肿瘤坏死因子。 此外，最近还发现了一种新的单核细胞因子， 并克隆了一个已命名为巨噬细胞炎性蛋白的基因 (MIP)。该蛋白可在体外诱导中性粒细胞迁移 在活体内。 在下一个赠款期间，对cachectin/TNF生产的研究， 体内外作用机制及对其作用机制的专门分析 它在促进恶病质和休克方面的作用将继续下去。这些 研究将包括详细分析以下几个控制点 脂蛋白脂酶的转录和翻译与葡萄糖 3T3-LL细胞中的转运蛋白。可能存在的相互作用 Cachectin/TNF与其他细胞因子(IL-1和干扰素-γ)联合应用 将对体内诱发恶病质进行评估。大鼠的动物模型 恶病质也将被检查恶病质/肿瘤坏死因子的可能作用。 通过注射抗cachectin抗体。进一步的工作也在进行中 与MIP一起计划以确定其他生物功能及其 与其他单核细胞的关系。此外，搜索将会 继续，对于巨噬细胞产生的其他单核细胞反应 为了入侵。这些研究应该会给我们提供新的见解 慢性感染相关恶病质的治疗。

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. A macrophage product, cachextia, 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-Ll pre-adipocytes in vitro. has been recently isolated. Microsequencing and subsequent cloning of mouse cachectin revealed that cachectin was identical to tumor necrosis factor (TNF). During the past few years, a number of biological activities associated with cachectin have been identified. These have included the ability to selectively turn off transcription of specific anabolic genes, promote anorexia, weight loss and anemia, induce fever, hemorrhagic necrosis, tubular necrosis and lethal shock. Antibodies to cachectin/TNF can prevent the lethality of mice to endotoxin and baboons to lethal septicemia. It thus appears that host overreacts to invasion and produces toxic amounts of cachectin/TNF. In addition, a new monokine has been recently identified, isolated and cloned which has been named macrophage inflammatory protein (MIP). This protein can elicit neutrophil migration in vitro and in vivo. In the next grant period, studies of cachectin/TNF production, mechanism of action in vitro and in vivo with special analysis on its role in promoting cachexia and shock, will be continued. These studies will include detailed analysis of control points for transcription and translation of lipoprotein lipase and the glucose transporter in 3T3-Ll cells. The possible interaction of cachectin/TNF with other cytokines (IL1 and Interferon gamma) of inducing cachexia in vivo will be assessed. Animal models of cachexia will also be examined for possible role of cachectin/TNF by administering anti-cachectin antibodies. Further work is also planned with MIP to determine other biological functions and its relationship to other monokines. In addition, a search will continue, for other monokines produced by macrophages in response to invasion. These studies should give new insight into therapeutics of the cachexia associated with chronic infections.