MIXED ASSOCIATIONS OF COMPLEMENT USING LIGHT SCATTERING

使用光散射的补体混合关联

• 批准号: 3135020
• 负责人: JAMES ZIMMERMAN
• 金额: $ 10.56万
• 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/3135020
• 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.

调查的目的是制造一种旨在迅速提供帮助的工具 分析NA+MB类型的混合关联产生AnBm。这个单位将 由高效液相梯度混合器、流通式小角度 激光散射式测光仪和专用计算机系统 控制实验，收集和分析实验结果。这个 仪器将能够快速生成三维表面， 作为坐标的两个总蛋白质浓度和 产生的重量-平均分子量，并分析这个表面在 缔合常数和化学计量的术语。 最初要研究的蛋白质系统是相互作用 B因子与不同形式的蛋白C3在交替途径中的作用 补充语。这一途径提供了一种(主要)非抗体的机制 依赖免疫反应。这种相互作用还直接涉及到 “无条件”透析患者的中性粒细胞减少反应 膜和人工材料后免疫效力降低 都被植入了。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 扩散。B因子、C3因子的相互作用直接牵连 神经性厌食症的生化问题。加强 这个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，目前还没有人能够 去找一个B因子缺失的案例。 拟议的文书本身很重要，因为它将允许 其他调查人员将检查其他具有重要生理意义的混合 大分子之间的缔合。调查的重点是 B因子与C3的不同形式的相互作用(在较长的时间内 从长远来看，其他补充因素，如H和P)对ITS很重要 尝试了解相互竞争的交互在 这段免疫区域。