Analysis of the regulation of complement activation

补体激活调节分析

• 批准号: 6886329
• 负责人: Amy Anne Caudy
• 金额: $ 1.26万
• 依托单位: WASHINGTON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-03-01 至 2005-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6886329
• 关键词: RNA interference; cell line; cell membrane; clinical research; complement pathway; complement receptor; fluorescence resonance energy transfer; gene induction /repression; membrane proteins; microscopy; postdoctoral investigator; receptor expression; technology /technique development

DESCRIPTION (provided by applicant): Complement is a group of plasma proteins that provide innate immunity through the targeting and degradation of non-self antigens and additionally cooperate with the immune system to destroy targets that are bound by antibodies. To control complement activity, cells express several membrane proteins, including CD46 (membrane cofactor protein; MCP), CD55 (decay accelerating factor; DAF) and CD59 (protectin). Recently, deficiency in a complement regulatory protein, CD46, was linked to a familial type of hemolytic uremic syndrome, a disease caused by complement attack in the blood vessels of the kidney. Surprisingly, three of the four affected families were heterozygous for CD46 deficiency, suggesting that levels of complement regulators are extremely important. Using RNA interference (RNAi), cell lines expressing varying levels of complement regulators will be created and tested to examine the relationship between regulator levels and complement attack. Second, the distribution of complement regulators and effectors at the cell surface will be examined using microscopy. Finally, a RNAi-based screen will be developed to identify pathways that affect the rate of complement deposition at the cell surface.

说明(申请人提供)：补体是一组血浆蛋白，通过靶向和降解非自身抗原提供先天免疫，并与免疫系统合作摧毁与抗体结合的目标。为了控制补体活性，细胞表达多种膜蛋白，包括CD46(膜辅因子蛋白)、CD55(衰变加速因子)和CD59(保护素)。最近，补体调节蛋白CD46的缺乏与一种家族性溶血性尿毒症综合征有关，这是一种由肾脏血管中的补体攻击引起的疾病。令人惊讶的是，四个受影响的家庭中有三个是CD46缺乏的杂合子，这表明补体调节水平极其重要。利用RNA干扰(RNAi)，将创建并测试表达不同水平的补体调节因子的细胞系，以检查调节因子水平与补体攻击之间的关系。其次，将用显微镜检查补体调节剂和效应器在细胞表面的分布。最后，将开发一种基于RNAi的筛选，以确定影响细胞表面补体沉积速度的途径。