MIXED ASSOCIATIONS OF COMPLEMENT USING LIGHT SCATTERING

使用光散射的补体混合关联

• 批准号: 3135022
• 负责人: JAMES ZIMMERMAN
• 金额: $ 9.21万
• 依托单位: CLEMSON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1986
• 资助国家: 美国
• 起止时间: 1986-09-01 至 1989-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3135022
• 关键词: biomedical automation; chemical association; complement; complement pathway; high performance liquid chromatography; lasers; light scattering; molecular weight; properdin; stoichiometry

The investigation intends to build an instrument designed to help rapidly analyze mixed associations of the type nA+ mB yields AnBm. This unit will be composed of an HPLC gradient mixing device, a flow-through low angle laser light scattering photometer, and a dedicated computer system to both control the experiment and to collect and analyze the results. The instrument will be able to quickly generate a three dimensional surface, having as coordinates the two total protein concentrations and the resulting weight-average molecular weights, and to analyze this surface in terms of association constants and stoichiometries. The protein system to initially be examined is the interaction between Factor B and the different forms of protein C3 in the alternative pathway of complement. This pathway provides a mechanism of (largely) non-antibody dependent immune response. This interaction is also directly involved in the neutropenia response of patients exposed to "unconditioned" dialysis membranes and in lowered immune effectiveness after artificial materials are implanted. Products resulting from these associations are also implicated in decreasing secretion of B cell antibodies, activating suppressor T cells, inhibiting helper T cells and suppressing T cell proliferation. The Factor B, C3 interaction has been directly implicated in the biochemical problems of anorexia nervosa. Reinforcing the importance of this protein system is the observation that, despite the many complement component genetic deficiencies known, no one yet has been able to find a case where Factor B is missing. The proposed instrument is important in its own right because it will allow other investigators to examine other physiologically important mixed associations between macromolecules. The investigation centered on the interaction of Factor B with the different forms of C3 (and in the longer term, other complement factors such as H and P) is important for its attempt to understand the relative roles of the competing interactions in this segment of the immune regions.

这项调查旨在建立一种工具， 分析nA+ mB类型的混合关联产生AnBm。 这个单位将 由HPLC梯度混合装置、流通式低角度 激光光散射光度计，以及专用的计算机系统， 控制实验并收集和分析结果。 的 仪器将能够快速生成三维表面， 以两个总蛋白浓度和 得到的重均分子量，并分析这个表面， 缔合常数和化学计量的术语。 首先要研究的蛋白质系统是 旁路途径中因子B和不同形式的蛋白质C3 的补充。 该途径提供了一种（很大程度上）非抗体机制， 依赖性免疫反应 这种互动也直接涉及到 暴露于“非条件”透析的患者的中性粒细胞减少反应 膜和人工材料后降低免疫效力 被植入体内 由这些协会产生的产品也 涉及减少B细胞抗体的分泌，激活 抑制性T细胞、抑制性辅助性T细胞和抑制性T细胞 增殖 因子B、C3的相互作用直接涉及 神经性厌食症的生化问题 加强 这种蛋白质系统的重要性是观察到，尽管有许多 已知的补体成分遗传缺陷，还没有人能够 来寻找因子B缺失的情况。 拟议的文书本身就很重要，因为它将允许 其他研究人员检查其他生理上重要的混合 大分子之间的联系。 调查集中在 因子B与不同形式的C3的相互作用（并且在较长时间内 术语，其他补体因子如H和P）对于其 试图理解竞争相互作用的相对作用， 这部分免疫区