AUTACOIDS AS PHARMACOLOGIC MODIFIERS OF HUMAN IMMUNITY

该提案试图确定生物学重要性和治疗性 更全面地了解自体免疫的潜力 这一建议有两个基石：1） 观察到一些炎症介质可调节免疫力;以及 2)选择性炎症介质的化学修饰 （组胺和儿茶酚胺）可导致组织形成和影响 特异性免疫调节剂 此外，研究表明， 的小鼠系统，组胺的来源可能是淋巴细胞内， 组胺的释放机制可能是 复杂但可控且有组织;这两种受体 所提到的autacoids非随机地分布在 自体素效应的表达依赖于细胞的 环境中的淋巴细胞和免疫应答阶段;以及 自体免疫对细胞亚群及其生理功能的影响， 互动是可能的。 该研究试图：1）确定 小鼠的数据是否可以通过使用 人细胞在体外和组胺和儿茶酚胺以及它们的 同源物和共轭物作为实验探针;和2）设置阶段 确定使用同系物的适当性和可行性， 作为治疗性免疫调节剂的类愈伤组织素缀合物。

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.