HEPATOCYTE-MONOCYTE INTERACTION IN ACUTE INFLAMMATION

急性炎症中的肝细胞-单核细胞相互作用

• 批准号: 3136591
• 负责人: GERALD M FULLER
• 金额: $ 10.63万
• 依托单位: UNIVERSITY OF ALABAMA AT BIRMINGHAM
• 依托单位国家: 美国
• 财政年份: 1986
• 资助国家: 美国
• 起止时间: 1986-01-01 至 1988-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3136591
• 关键词: acute disease /disorder; aminoacid; carbohydrates; inflammation; liver cells; macrophage; monocyte; physical chemical interaction; tissue /cell culture

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.

任何病因的急性炎症都会引发众所周知的序列 生物体内的分子和细胞变化。 包含在这个 反应是许多物质的合成和分泌的改变 肝源性血浆蛋白。 我们最近证明了 单核细胞和巨噬细胞在被激活时会分泌一种蛋白质因子， 显着影响几种肝细胞来源血浆的合成 蛋白质。 该提案的长期目标是 (a) 隔离和 对这种常规蛋白质进行化学表征，（b）了解什么 触发单核细胞中调节剂的合成，并且（c） 确定调节蛋白如何刺激肝脏产生 某些血浆蛋白。 将开展多项此类研究 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， 我们开发了一种特定的定量生物测定法，将用于 净化肝刺激因子。 这些研究的结果将 提供有关重要化学物质和作用方式的新信息 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于以下原因发生的 创伤和疾病状态的数量、化学知识和 引起反应的因素的功能对于 了解炎症的分子机制。