Analysis of the regulation of complement activation

描述（由申请人提供）：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，并与免疫系统合作破坏被抗体结合的靶标。为了控制补体活性，细胞表达多种膜蛋白，包括CD46（膜辅助因子蛋白；MCP）， CD55（衰变加速因子；DAF）和CD59（保护蛋白）。最近，一种补体调节蛋白CD46的缺乏与一种家族型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缺乏症的杂合子，这表明补体调节因子的水平非常重要。使用RNA干扰（RNAi），将创建和测试表达不同水平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，将使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，我们将开发一种基于rnai的筛选方法，以确定影响细胞表面补体沉积速率的途径。

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.