Neale T J, Rüger B M, Macaulay H, Dunbar P R, Hasan Q, Bourke A, Murray-McIntosh R P, Kitching A R
Department of Medicine, Wellington School of Medicine, New Zealand.
Am J Pathol. 1995 Jun;146(6):1444-54.
The role of tumor necrosis factor alpha (TNF-alpha) was examined in biopsy-proven glomerulonephritis by immunohistochemistry, in situ hybridization, immunogold electron microscopy, immunoassay in serum and urine, and urinary immunoblot. Striking glomerular capillary wall and visceral glomerular epithelial cell TNF-alpha protein staining was observed in all cases of membranous nephropathy and membranous lupus nephropathy. Staining was less frequently observed in crescentic glomerulonephritis and in isolated cases of other histological subtypes of glomerulonephritis, usually in association with glomerular macrophages. By immunogold electron microscopy TNF-alpha was localized in membranous nephropathy within the visceral glomerular epithelial cells, and also in the glomerular basement membrane, especially in relation to immune deposits. In situ hybridization localized TNF-alpha mRNA exclusively to glomerular epithelial cells in all biopsies with membranous morphology but not in other histological subtypes. Concentrations of TNF-alpha were significantly increased compared with normal controls in the urine of patients with membranous nephropathy and with crescentic glomerulonephritis. The expression of TNF-alpha by glomerular epithelial cells exclusively and universally in biopsies showing a membranous morphology strongly suggests this cytokine has a role in the pathogenesis of membranous nephropathy.
通过免疫组织化学、原位杂交、免疫金电子显微镜、血清和尿液免疫测定以及尿液免疫印迹法，对经活检证实的肾小球肾炎中肿瘤坏死因子α（TNF-α）的作用进行了研究。在所有膜性肾病和膜性狼疮性肾病病例中，均观察到显著的肾小球毛细血管壁和肾小球脏层上皮细胞TNF-α蛋白染色。在新月体性肾小球肾炎和其他组织学亚型的孤立病例中，染色较少见，通常与肾小球巨噬细胞有关。通过免疫金电子显微镜，TNF-α定位于膜性肾病的肾小球脏层上皮细胞内，也定位于肾小球基底膜，尤其是与免疫沉积物相关的部位。原位杂交将TNF-α mRNA仅定位于所有具有膜性形态的活检组织中的肾小球上皮细胞，而在其他组织学亚型中则未未未未发现。与正常对照组相比，膜性肾病和新月体性肾小球肾炎患者尿液中TNF-α的浓度显著升高。在显示膜性形态的活检组织中，肾小球上皮细胞仅普遍表达TNF-α，这强烈表明该细胞因子在膜性肾病的发病机制中起作用。
