Abrera-Abeleda M A, Xu Y, Pickering M C, Smith R J H, Sethi S
Department of Otolaryngology, University of Iowa, Iowa City, Iowa, USA.
Kidney Int. 2007 Jun;71(11):1142-7. doi: 10.1038/sj.ki.5002235. Epub 2007 Apr 4.
Complement factor D is a serine protease essential for the activation of the alternative pathway and is expressed in the kidney, adipocytes, and macrophages. Factor D is found at relatively high levels in glomeruli suggesting that this component of the complement cascade could influence renal pathophysiology. In this study, we utilize mice with a targeted deletion of the activating complement factor D gene and compare these results to mice with targeted deletion of the inhibitory complement factor H gene. Eight-month-old mice with a deleted factor D gene spontaneously develop albuminuria and have reduced creatinine clearance due to mesangial immune complex glomerulonephritis. These mesangial deposits contain C3 and IgM. In contrast to the mesangial location of the immune deposits in the factor D-deficient mice, age-matched factor H-deficient mice develop immune deposits along the glomerular capillary wall. Our observations suggest that complement factor D or alternative pathway activation is needed to prevent spontaneous accumulation of C3 and IgM deposits within the mesangium. Our studies show that the complement factor D gene knockout mice are a novel model of spontaneous mesangial immune complex glomerulonephritis.
补体因子D是替代途径激活所必需的丝氨酸蛋白酶，在肾脏、脂肪细胞和巨噬细胞中表达。在肾小球中发现因子D的水平相对较高，这表明补体级联反应的这一成分可能影响肾脏病理生理学。在本研究中，我们利用靶向缺失激活补体因子D基因的小鼠，并将这些结果与靶向缺失抑制性补体因子H基因的小鼠进行比较。8月龄因子D基因缺失的小鼠由于系膜免疫复合物性肾小球肾炎而自发出现蛋白尿，肌酐清除率降低。这些系膜沉积物含有C3和IgM。与因子D缺陷小鼠免疫沉积物位于系膜不同，年龄匹配的因子H缺陷小鼠在肾小球毛细血管壁处形成免疫沉积物。我们的观察结果表明，需要补体因子D或替代途径激活来防止系膜内C3和IgM沉积物的自发积累。我们的研究表明，补体因子D基因敲除小鼠是自发系膜免疫复合物性肾小球肾炎的一种新模型。
