AUTACOIDS AS PHARMACOLOGIC MODIFIERS OF HUMAN IMMUNITY

这项建议试图确定生物重要性和治疗 更透彻地了解耳甲状软骨作为免疫的可能性 人类体内的调节器。这项建议有两个基石：1) 观察到一些炎症介质可能调节免疫；以及 2)选定的炎症介质的化学修饰 (组胺和儿茶酚胺)可导致组织的形成和影响 特定的免疫调节剂。此外，这一点在研究中变得越来越明显 组胺的来源可能在淋巴细胞内的小鼠系统 除了肥大细胞之外；组胺释放机制可以是 复杂但可控且有条理的；这两种受体 所提到的类耳石是非随机分布在 淋巴组织细胞；海绵样体效应的表达依赖于 环境中的淋巴细胞和免疫反应阶段；以及 类胡萝卜素对细胞亚群及其生理功能的影响 互动是可能的。拟议的研究试图：1)确定 老鼠的数据是否可以通过使用 体外培养的人细胞和组胺、儿茶酚胺及其受体 同系物和偶联物作为实验探针；2)搭建舞台 为了确定使用同系物和 作为治疗性免疫调节剂的金盏花素结合物。

This proposal attempts to determine the biologic importance and therapeutic potential of a more thorough understanding of autacoids as immune modulators in man. There are two cornerstones of this proposal: 1) the observation that some mediators of inflammation may modulate immunity; and 2) that chemical modification of selected mediators of inflammation (histamine and catecholamines) can result in formation of tissue and effect specific immune modulators. Furthermore, it is becoming evident in studies of mouse systems that sources of histamine may be within lymphocytes in addition to mast cells; that release mechanisms for histamine may be complex but controllable and organized; that receptors for the two autacoids mentioned are non-randomly distributed on subsets of lymphyocytes; that expression of autacoid effects are dependent on the lymphocytic cells in the environment and the stage of immune response; and that the effects of autacoids on subsets of cells and their physiologic interactions are possible. The proposed study attempts to: 1) determine whether the data from mice can be extrapolated and extended to man by using human cells in vitro and both histamine and catecholamines as well as their congeners and conjugates as experimental probes; and 2) to set the stage for determining the appropriateness and feasibility of using congeners and conjugates of autacoids as therapeutic immune modulators.