Satoh M, Kumar A, Kanwar Y S, Reeves W H
Department of Medicine, Thurston Arthritis Research Center, University of North Carolina, Chapel Hill 27599-7280, USA.
Proc Natl Acad Sci U S A. 1995 Nov 21;92(24):10934-8. doi: 10.1073/pnas.92.24.10934.
The pathogenesis of systemic lupus erythematosus is thought to be primarily under genetic control, with environmental factors playing a secondary role. However, it has been shown recently that intraperitoneal injection of pristane (2,6,10,14-tetramethylpentadecane) induces autoantibodies typical of lupus in BALB/c mice, a strain not usually considered to be genetically susceptible to the disease. In this study, the induction of autoimmune disease by pristane was investigated. BALB/c mice receiving pristane were tested for autoantibody production and histopathological evidence of glomerulonephritis. Six of 11 mice developed IgM anti-single-stranded DNA antibodies shortly after receiving pristane and 4 developed IgM anti-histone antibodies, but anti-double-stranded DNA antibodies were absent. IgG anti-DNA and anti-histone antibodies were absent. In contrast, the lupus-associated anti-nuclear ribonucleoprotein/Sm and anti-Su autoantibodies produced by these mice were predominantly IgG. In addition to autoantibodies, most of the mice developed significant proteinuria. Light microscopy of the kidney showed segmental or diffuse proliferative glomerulonephritis. Electron microscopy showed subepithelial and mesangial immune-complex deposits and epithelial foot process effacement. Immunofluorescence revealed striking glomerular deposition of IgM, IgG, and C3 with a mesangial or mesangiocapillary distribution. Thus, pristane induces immune-complex glomerulonephritis in association with autoantibodies typical of lupus in BALB/c mice. These data support the idea that lupus is produced by an interplay of genetic and environmental factors and that unlike the MRL or (NZB x W)F1 mouse models, in which genetic susceptibility factors are of primary importance, environmental factors are of considerable importance in the autoimmune disease of pristane-treated BALB/c mice.
系统性红斑狼疮的发病机制被认为主要受基因控制，环境因素起次要作用。然而，最近有研究表明，腹腔注射 pristane（2,6,10,14 - 四甲基十五烷）可在 BALB/c 小鼠中诱导出狼疮典型的自身抗体，而该品系小鼠通常不被认为对这种疾病具有遗传易感性。在本研究中，对 pristane 诱导自身免疫性疾病的情况进行了调查。对接受 pristane 的 BALB/c 小鼠检测了自身抗体产生情况以及肾小球肾炎的组织病理学证据。11 只小鼠中有 6 只在接受 pristane 后不久产生了 IgM 抗单链 DNA 抗体，4 只产生了 IgM 抗组蛋白抗体，但未检测到抗双链 DNA 抗体。未检测到 IgG 抗 DNA 和抗组蛋白抗体。相比之下，这些小鼠产生的与狼疮相关的抗核核糖核蛋白/Sm 和抗 - Su 自身抗体主要为 IgG。除自身抗体外，大多数小鼠出现了明显的蛋白尿。肾脏的光学显微镜检查显示节段性或弥漫性增殖性肾小球肾炎。电子显微镜检查显示上皮下和系膜免疫复合物沉积以及上皮足突消失。免疫荧光显示 IgM、IgG 和 C3 在肾小球中有明显沉积，呈系膜或系膜毛细血管分布。因此，pristane 在 BALB/c 小鼠中诱导出与狼疮典型自身抗体相关的免疫复合物性肾小球肾炎。这些数据支持了狼疮是由遗传和环境因素相互作用产生的观点，并且与 MRL 或（NZB×W）F1 小鼠模型不同，在后者中遗传易感性因素至关重要，而在 pristane 处理的 BALB/c 小鼠的自身免疫性疾病中，环境因素具有相当重要的作用。
