ACTIVATION OF THE COMPLEMENT SYSTEM

补体系统的激活

• 批准号: 3129583
• 负责人: IRMA GIGLI
• 金额: $ 18.05万
• 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 1989-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3129583
• 关键词: complement; complement inhibitors; complement pathway; guinea pigs; immune complex; immunochemistry; immunoregulation; laboratory rabbit; photochemistry; protein structure function

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 C4 和 C3 分子通过经典或 分别为经典途径和替代途径。 片段交互 这两个分子与抗原抗体复合物和表面 不同细胞类型上的受体可调节补体依赖性 功能。 虽然已经积累了大量的知识 替代途径，与经典途径相关的相同信息 不太完整。 本申请提出的研究主要针对 描述所涉及蛋白质的一些结构和功能方面 蛋白质的形成以及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。 具体来说，我们计划 1) 进一步描述主要特征 在激活和失活过程中产生的 C4 切割片段 分子。 片段将被分离至同质并进行 化学分析。 2) 伴随的构象变化分析 C4 的酶促转化和降解失活 方法。 这些研究将使用差异表面标记，这将 允许识别参与分子的不同区域 这些功能上的变化。 3）结构要求调查 用于对照蛋白 C4-bp 和 I 与液相的相互作用 和表面结合的C4b。 4) 观察到异常蛋白质 病理条件下的人血清中，C4肾炎因子，具有 促使研究确定正常血清中的一种蛋白质能够 稳定 C4b2a 酶。 该蛋白的鉴定将 完成对形成、功能和调节的类比 经典和替代 C3 转化酶。 申请的第二部分 上述研究感兴趣的是激活 补体系统由含有 IgA 和 IgM 的免疫复合物组成。 此外， 非免疫机制激活补体的机制 将调查使用光毒性化学品的情况。