MACROPHAGE ACTIVATION FOR TUMOR CELL KILLING

该计划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。这个 该组织的工作将由该领域的一位知名科学家领导，他 也是一位经验丰富的生物医学管理人员，史蒂芬·W·罗素博士。 第一个项目负责人大卫·C·莫里森博士的目标是 确定内毒素如何启动激活。他将专注于受体 他发现的内毒素的蛋白质，以及疏水性 内毒素与巨噬细胞膜之间的相互作用可能有助于 启动信号(S)以进行激活。铃木忠雄博士(项目 领导人2)将研究内毒素与巨噬细胞结合的假说 通过触发磷脂酰肌醇激活蛋白激酶C(PKC) 中性细胞内蛋白水解酶的周转和激活， Calain，然后裂解并激活PKC。罗素博士(项目负责人 #3)将作为他的团队的目标，准确地描述类型I 干扰素影响激活。他的重点将主要放在 影响细胞溶解机制的诱导和表达，以及 巨噬细胞正、负自分泌/旁分泌调节作用 产生干扰素。将定义相关的监管机制。Dr。 Michael J.Parmely(项目负责人#4)和他的团队将专注于这个角色 转化生长因子-β在调节小鼠巨噬细胞活化中的作用。 具体地说，他将描述生产的潜伏性和主动性 小鼠巨噬细胞转化生长因子-β的形式，决定转化生长因子-β的活性 影响激活的巨噬细胞介导的杀瘤活性，以及 确定这些监管效应在多大程度上是自分泌 起源。核心部分，包括 罗素博士的监督，将是最大限度地整合 从而获得了各个项目之间的协同效应。《核心》 组件的研究计划协调员将提供行政管理 支持，旨在使项目成为 作为一个整体，而不是作为独立的努力。因为自然的 项目和必要的核心职能的互补性 将由核心组件提供，很难想象集团如何 作为任何计划的一般目标寻求的互动和协同 该项目将不会在这里实现。

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.