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MIXED ASSOCIATIONS OF COMPLEMENT USING LIGHT SCATTERING

使用光散射的补体混合关联

基本信息

批准号：
3135023
负责人：
JAMES ZIMMERMAN
金额：
$ 8.15万
依托单位：
CLEMSON UNIVERSITY
依托单位国家：
美国
项目类别：
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/3135023
关键词：
biomedical automation chemical association complement complement pathway high performance liquid chromatography lasers light scattering molecular weight properdin stoichiometry

项目摘要

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.

该调查旨在建立一种旨在快速帮助分析 nA+ mB 类型的混合关联产生 AnBm。本单位将由HPLC梯度混合装置、流通式小角度混合装置组成激光光散射光度计和专用计算机系统控制实验并收集和分析结果。这仪器将能够快速生成三维表面，坐标为两个总蛋白浓度和所得重均分子量，并分析该表面缔合常数和化学计量条件。最初要检查的蛋白质系统是之间的相互作用旁路途径中的因子 B 和不同形式的蛋白 C3 的补体。该途径提供了（很大程度上）非抗体的机制依赖性免疫反应。这种互动也直接涉及到接受“无条件”透析的患者的中性粒细胞减少反应人工材料后细胞膜和免疫效果降低被植入。这些协会产生的产品也参与减少 B 细胞抗体的分泌，激活抑制性 T 细胞、抑制辅助性 T 细胞和抑制性 T 细胞增殖。因子 B、C3 相互作用直接涉及神经性厌食症的生化问题。加强该蛋白质系统的重要性在于观察到，尽管有许多补体成分的遗传缺陷已知，但尚未有人能够找到因子 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缔合。调查的重点是因子 B 与不同形式的 C3 的相互作用（并且在较长的时间内）术语，其他补体因素，例如 H 和 P）对其很重要尝试理解竞争相互作用的相对作用免疫区域的这一部分。