MACROPHAGE ACTIVATION FOR TUMOR CELL KILING

本项目的总体目标是了解如何 巨噬细胞被激活/失活以杀死肿瘤细胞。 的 该小组的工作将由该领域的一位知名科学家领导， 也是一位经验丰富的生物医学管理人员，斯蒂芬W。Russell. 第一个项目负责人大卫博士的目标。莫里森是 确定LPS如何启动激活。 他将专注于受体 他发现的LPS蛋白质，以及疏水蛋白质， LPS和巨噬细胞膜之间的相互作用可能有助于 启动用于激活的信号。 Tsuneo Suzuki博士（项目 Leader #2）将研究LPS与巨噬细胞结合的假设， 通过触发磷脂酰肌醇激活蛋白激酶C（PKC） 周转以及中性细胞内蛋白酶的活化， 钙蛋白酶，然后切割并激活PKC。 Russell博士（项目负责人 #3）将作为他的小组的目标，精确地描绘I型如何 干扰素影响活化。 他的重点将主要放在如何 细胞溶解机制的诱导和表达受到影响， 巨噬细胞的正性和负性自分泌/旁分泌调节作用- 生产IFN。 将确定相关的管理机制。 博士 Michael J. Parmely（项目负责人#4）和他的团队将专注于 TGF-β在调节小鼠巨噬细胞活化方面的作用。 具体而言，他将表征生产的潜伏和主动 通过小鼠巨噬细胞的TGF-β形式，确定如何激活TGF-β 影响活化的巨噬细胞介导的杀肿瘤活性， 确定这些调节作用是自分泌的程度 起源 核心构成部分包括行政支助， 罗素博士的监督，将是最大整合的手段， 因此，在各种项目之间获得协同作用。 核心 组件的研究计划协调员将提供行政 支持，旨在使项目的功能作为一个组成部分， 一个整体，而不是作为独立的努力。 由于自然 项目的互补性和基本的中心职能， 将由核心组件提供，很难想象该集团如何 相互作用和协同作用是任何计划的总目标 这个项目不会在这里实现。

The overall objective of this program project is to understand how macrophages become activated/deactivated for tumor cell killing. The group's efforts will be led by an established scientist in the field, who is also an experienced biomedical administrator, Dr. Stephen W. Russell. The objective of the first project leader, Dr. David C. Morrison, is to establish how LPS initiates activation. He will focus on the receptor proteins for LPS that he has discovered, as well as hydrophobic interactions between LPS and macrophage membranes that may contribute to initiation of the signal(s) for activation. Dr. Tsuneo Suzuki (project leader #2) will investigate the hypothesis that LPS binding to macrophages activates protein kinase C (PKC) by triggering phosphatidylinositol turnover as well as activation of the neutral intracellular proteinase, calpain, which then cleaves and activates PKC. Dr. Russell (project leader #3) will have as his group's goal the delineation of precisely how type I interferons affect activation. His emphasis will primarily be on how the induction and expression of cytolytic mechanisms are affected, as well as positive and negative autocrine/paracrine regulatory effects of macrophage- produced IFN. The associated regulatory mechanisms will be defined. Dr. Michael J. Parmely (project leader #4) and his group will focus on the role that TGF-beta has in regulating the activation of mouse macrophages. Specifically, he will characterize the production of latent and active forms of TGF-beta by mouse macrophages, determine how active TGF-beta affects the mediation of tumoricidal activity by activated macrophages, and ascertain the extent to which these regulatory effects are of autocrine origin. The Core Component, consisting of administrative support under the supervision of Dr. Russell, will be the means by which maximal integration and, therefore, synergism among the various projects is obtained. The Core Component's Research Program Coordinator will provide administrative support that is designed to make the projects function as integral parts of a whole, rather than as independent endeavors. Because of the natural complementarity of the projects and the essential, central functions that will be provided by the Core Component, it is hard to imagine how the group interactions and synergism that are sought as general goals of any program project will not be realized here.