ACTIVATION OF THE COMPLEMENT SYSTEM

补体系统的激活

• 批准号: 3129581
• 负责人: IRMA GIGLI
• 金额: $ 16.49万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN DIEGO
• 依托单位国家: 美国
• 财政年份: 1982
• 资助国家: 美国
• 起止时间: 1982-09-15 至 1988-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3129581
• 关键词: chemical structure function; complement; complement inhibitors; complement pathway; immune complex; immunochemistry; immunoregulation; photochemistry

Activation of the complement system results in a selective and control fragmentation of the C4 and C3 molecules via the classical, or the classical and alternative pathways respectively. Interaction of fragments of these two molecules with antigen-antibody complexes and with surface receptors on different cell types serve to modulate complement-dependent functions. Although a great deal of knowledge has been accumulated on the alternative pathway, the same information relating to the classical pathway is less complete. This application proposes studies aimed primarily at delineating some structural and functional aspects of the proteins involved in the formation and some structural and functional aspects of the proteins involved in the formation and function of the classical pathway C3 convertase. Specifically, we plan to 1) Further characterize the major cleavage fragments of C4 produced during activation and inactivation of the molecule. The fragments will be isolated to homogeneity and subjected to chemical analysis. 2) Analysis of the conformational changes accompanying the enzymatic conversion and degradative inactivation of C4 by various methods. These studies will use differential surface labeling which will allow the identification of distinct regions of the molecule involved in these functional changes. 3) Investigation of the structural requirements for the interaction of the control proteins, C4-bp and I, with fluid phase and surface bound C4b. 4) The observation of an abnormal protein seen in humans serum under pathological conditions, C4 nephritic factor, has prompted studies to identify a protein in normal serum capable of stabilizing the C4b2a enzyme. The identification of this protein would complete the analogies to the formation, function and regulation of the classical and alternative C3 convertases. A second part of the application to which the above studies are of interest involves the activation of the complement system by IgA and IgM containing immune complexes. In addition, the mechanisms of complement activation by a non-immunologic mechanism using phototoxic chemicals will be investigated.

补体系统的激活导致选择性和控制性 C4和C3分子的经典碎裂，或 分别是经典路径和替代路径。碎片之间的相互作用 这两个分子分别与抗原-抗体复合体和表面 不同细胞类型上的受体调节补体依赖 功能。虽然在这方面已经积累了大量知识 替代途径，与经典途径相关的相同信息 就不那么完整了。本申请提出的研究主要旨在 描述了所涉及的蛋白质的一些结构和功能方面 在蛋白质的形成和一些结构和功能方面 参与经典途径C3的形成和功能 转化酶。具体地说，我们计划1)进一步描述主要的 C4在激活和失活过程中产生的切割片段 分子。这些碎片将被分离到同质状态并经受 化学分析。2)伴随的构象变化分析 不同菌种对C4的酶转化和降解失活 方法：研究方法。这些研究将使用差异表面标记，这将 允许识别所涉及的分子的不同区域 这些功能变化。3)结构要求调查 对于控制蛋白C4-BP和I与液体相的相互作用 和表面结合的C4b。4)观察到一种异常蛋白质 病理条件下的人血清C4肾病因子 促使研究发现正常血清中的一种蛋白质能够 稳定C4b2a酶。这种蛋白质的鉴定将会 完成对细胞的形成、功能和调节的类比 经典的和替代的C3转化酶。应用程序的第二部分 上述研究感兴趣的研究涉及激活 由含有IgA和IgM的免疫复合体组成的补体系统。此外, 补体激活的非免疫学机制 将对使用光毒性化学物质进行调查。