Abnormal Immune Complex Processing and Spontaneous Glomerulonephritis in Complement Factor H-Deficient Mice with Human Complement Receptor 1 on Erythrocytes
Abnormal Immune Complex Processing and Spontaneous Glomerulonephritis in Complement Factor H-Deficient Mice with Human Complement Receptor 1 on Erythrocytes
复制标题
DOI：
10.4049/jimmunol.1000683
复制
发表时间：
2010-09-15
影响因子：
4.4
通讯作者：
Quigg, Richard J.
中科院分区：
文献类型：
--
作者：
Alexander, Jessy J.;Hack, Bradley K.;Quigg, Richard J.
人红细胞（Es）上的补体受体1（CR 1）和啮齿动物血小板上的补体因子H（CFH）执行免疫粘附，这是一种允许单核吞噬细胞系统处理携带C3的免疫复合物（IC）的功能。类似的免疫粘附发生在肾小球足细胞的CR 1在人类和CFH在啮齿动物。作为人类IC加工的模型，我们研究了全身缺乏CFH但在Es上具有人类CR 1的转基因小鼠。这些CR 1（hu）Tg/CFH-/-小鼠自发发生增生性肾小球肾炎，在慢性血清病模型中，通过异源脱铁铁蛋白主动免疫加速了这种情况。在CR 1（hu）Tg/CFH-/-小鼠中，含有Ag、IgG和C3的IC与Es结合。在这种情况下，肾小球中IC沉积增加，归因于ES上存在CR 1，以及血小板和足细胞上不存在CFH。在缺乏血浆CFH的情况下，积聚的IC激活补体，导致自发性和慢性血清病诱导的增殖性肾小球肾炎。这些发现说明了血细胞和肾小球中补体依赖性IC加工的复杂性，以及CFH作为血浆补体调节剂的重要性。免疫学杂志，2010，185：3759-3767。
Complement receptor 1 (CR1) on human erythrocytes (Es) and complement factor H (CFH) on rodent platelets perform immune adherence, which is a function that allows the processing of immune complexes (ICs) bearing C3 by the mononuclear phagocyte system. Similar immune adherence occurs in the glomerular podocyte by CR1 in humans and CFH in rodents. As a model for human IC processing, we studied transgenic mice lacking CFH systemically but with human CR1 on Es. These CR1(hu)Tg/CFH-/- mice spontaneously developed proliferative glomerulonephritis, which was accelerated in a chronic serum sickness model by active immunization with heterologous apoferritin. ICs containing Ag, IgG and C3 bound to Es in CR1(hu)Tg/CFH-/- mice. In this setting, there was increased IC deposition in glomeruli, attributable to the presence of CR1 on Es, together with the absence of CFH on platelets and podocytes. In the absence of plasma CFH, the accumulated ICs activated complement, which led to spontaneous and chronic serum sickness-induced proliferative glomerulonephritis. These findings illustrate the complexities of complement-dependent IC processing by blood cells and in the glomerulus, and the importance of CFH as a plasma complement regulator. The Journal of Immunology, 2010, 185: 3759-3767.