STRUCTURE & REGULATION OF HEPATOCYTE STIMULATING FACTOR

任何病因的急性炎症都会引发一系列公认的炎症反应， 生物体内的分子和细胞变化。 纳入本 反应是一种改变的合成和分泌的一些 肝源性血浆蛋白。 我们最近已经证明， 单核细胞和巨噬细胞在被激活时分泌一种蛋白因子， 显著影响几种肝细胞衍生血浆的合成 proteins. 这项建议的长远目标是（a）隔离和 化学表征这种常规蛋白质，（B）以了解 触发单核细胞中调节剂的合成，以及（c） 确定调节蛋白如何刺激肝脏产生 某些血浆蛋白 其中一些研究将在 在单层培养系统中使用肝细胞和单核细胞。 我们有 已经确定培养中的原代肝细胞对 单核细胞因子以类似于体内反应的方式。 此外，委员会还认为， 我们开发了一种特定的定量生物测定法， 纯化肝刺激因子。 这些研究的结果将 提供了新的信息，化学和作用方式的一个重要的 一种与急性炎症密切相关的调节蛋白 反应 由于急性炎症反应是由 创伤和疾病状态的数量，化学知识， 引起反应的因素的功能对于 了解炎症的分子机制。

Acute inflammation of any etiology initiates a well recognized sequence of molecular and cellular changes within an organism. Included in this response is an alteration the synthesis and secretion of a number of hepatically derived plasma proteins. We have recently demonstrated that monocytes and macrophages, when activated, secrete a protein factor which significantly effects the synthesis of several hepatocyte derived plasma proteins. The long range objective of this proposal is (a) to isolate and chemically characterize this regular protein, (b) to understand what triggers the synthesis of the regulator in the monocyte and (c) to determine how the regulator protein stimulates the hepatic production of certain plasma proteins. A number of these studies will be carried out using hepatocytes and monocytes in monolayer culture systems. We have already established that primary hepatocytes in culture respond to the monocytic factor in a manner analogous to in vivo response. Furthermore, we have developed a specific quantitative bioassay which will be used to purify the hepatic stimulating factor. Results from these studies will provide new information on the chemistry and mode of action of an important regulator protein that is intimately involved in the acute inflammatory reaction. Since an acute inflammatory reaction occurs as a result of a number of trauma and disease states, knowledge of the chemistry and function of the factor(s) involved in causing the response is crucial to understanding the molecular mechanism of inflammation.