Abe K, Miyazaki M, Koji T, Furusu A, Shioshita K, Tsukasaki S, Ozono Y, Harada T, Sakai H, Kohno S
Second Department of Internal Medicine, Nagasaki University School of Medicine, 1-7-1, Sakamoto, Nagasaki 852-5201, Japan.
Nephron. 2001 Mar;87(3):231-9. doi: 10.1159/000045920.
Complement activation is thought to be pathologically important in IgA nephropathy (IgAN). Although C3 deposition in the mesangium is found in IgAN, the origin of C3 is not clear. We recently demonstrated intraglomerular C3 synthesis in the human kidney; however, the activation and pathological role of locally synthesized C3 remains unclear. Here we performed nonradioactive in situ hybridization for C3 mRNA and immunohistochemistry for C3 and its activation products, such as C3d and membrane attack complex (MAC), to determine whether locally produced C3 in glomeruli was activated in IgA nephropathy.
Renal samples from 14 patients with IgAN and 5 with minimal change nephrotic syndrome (MCNS) were examined. Uninvolved portions of surgically removed kidneys with tumors served as normal controls.
C3 mRNA was not detected in glomeruli in control tissue and MCNS, but was strongly expressed in resident glomerular cells of IgAN, including mesangial cells, glomerular epithelial cells and the cells of Bowman's capsule. Examination of serial sections disclosed that more than 70% of cells positive for C3 mRNA were also stained for C3 protein, C3d, and MAC. Double staining for in situ hybridization and immunohistochemistry also revealed that those C3 mRNA signals were present in intraglomerular cells positive for C3. The expression of C3 mRNA and MAC in glomeruli correlated significantly with the degree of mesangial matrix expansion.
Our results demonstrated that locally synthesized C3 is activated in the glomeruli of IgAN and that its expression correlated with the severity of mesangial matrix expansion. These findings suggest that activation of C3 may be involved in tissue injury in IgAN through the formation of membrane attack complex.
补体激活被认为在IgA肾病（IgAN）中具有重要的病理意义。虽然在IgAN中发现系膜区有C3沉积，但C3的来源尚不清楚。我们最近证实了人肾内肾小球C3的合成；然而，局部合成的C3的激活及其病理作用仍不清楚。在此，我们进行了C3 mRNA的非放射性原位杂交以及C3及其激活产物如C3d和膜攻击复合物（MAC）的免疫组织化学检测，以确定IgA肾病中肾小球局部产生的C3是否被激活。
检测了14例IgAN患者和5例微小病变肾病（MCNS）患者的肾组织样本。手术切除的有肿瘤的肾脏未受累部分作为正常对照。
在对照组织和MCNS的肾小球中未检测到C3 mRNA，但在IgAN的肾小球固有细胞中强烈表达，包括系膜细胞、肾小球上皮细胞和鲍曼囊细胞。连续切片检查显示，超过70%的C3 mRNA阳性细胞也被C3蛋白、C3d和MAC染色。原位杂交和免疫组织化学双重染色也显示，那些C3 mRNA信号存在于C3阳性的肾小球内细胞中。肾小球中C3 mRNA和MAC的表达与系膜基质扩张程度显著相关。
我们的结果表明，局部合成的C3在IgA肾病的肾小球中被激活，其表达与系膜基质扩张的严重程度相关。这些发现提示，C3的激活可能通过膜攻击复合物的形成参与IgA肾病的组织损伤。
