Fujigaki Yoshihide, Muranaka Yoshinori, Sakakima Masanori, Ohta Isao, Sakao Yukitoshi, Fujikura Tomoyuki, Sun Yuan, Katafuchi Ritsuko, Joh Kensuke, Hishida Akira
The First Department of Medicine, Hamamatsu University School of Medicine, Hamamatsu, 431-3192, Japan.
Clin Exp Nephrol. 2008 Dec;12(6):432-9. doi: 10.1007/s10157-008-0095-9. Epub 2008 Oct 7.
Systemically podocytic infolding into the GBM which causes nonargyrophilic holes in the GBM in association with intra-GBM microstructures has been considered as a new pathological entity. However, its pathomechanisms are largely unknown.
We analyzed intra-GBM microstructures in an SLE patient with glomerulopathy associated with podocytic infolding by immunoelectron microscopy for vimentin (a marker for both podocyte and endothelium) and C5b-9 and by 3D reconstruction of transmission electron microscopy (TEM) images by computer tomography method.
Immunofluorescent study showed immunoglobulin deposition in a diffuse, capillary pattern; however, electron-dense deposits like stage 3 membranous nephropathy could be found only in some capillary loops by TEM in spite of the systemic existence of podocytic infolding and the intra-GBM microstructures. Three-dimensional reconstructed images of the TEM images revealed that some of the intra-GBM microstructures made connections with the podocyte. The clustered microstructures underneath the podocyte and their surroundings looked as a whole like the degraded part of podocyte in 3D reconstructed images. Immunoelectron microscopy showed that vimentin was positive in most intra-GBM microstructures. C5b-9 was positive along the entire epithelial side of the GBM and in some microstructures, suggesting that the podocytes may be attacked by C5b-9 and that the microstructures may contain C5b-9 bound cellular membranes.
Intra-GBM microstructures may be originated mainly from the podocyte. Podotyte and GBM injuries caused by C5b-9 attack to podocytes might contribute in part to podocytic infolding and intra-GBM microstructures in this case.
系统性足细胞内褶入肾小球基底膜(GBM),导致GBM出现非嗜银性孔洞并伴有GBM内微结构,这被认为是一种新的病理实体。然而,其发病机制尚不清楚。
我们通过免疫电子显微镜检测波形蛋白(足细胞和内皮细胞的标志物)和C5b-9,并采用计算机断层扫描方法对透射电子显微镜(TEM)图像进行三维重建,分析了一名患有与足细胞内褶相关的肾小球病的系统性红斑狼疮(SLE)患者的GBM内微结构。
免疫荧光研究显示免疫球蛋白呈弥漫性、毛细血管样沉积;然而,尽管存在系统性足细胞内褶和GBM内微结构,但通过TEM仅在一些毛细血管袢中发现了类似3期膜性肾病的电子致密沉积物。TEM图像的三维重建显示,一些GBM内微结构与足细胞相连。足细胞下方聚集的微结构及其周围在三维重建图像中整体看起来像足细胞的降解部分。免疫电子显微镜显示波形蛋白在大多数GBM内微结构中呈阳性。C5b-9在GBM的整个上皮侧及一些微结构中呈阳性,提示足细胞可能受到C5b-9的攻击,且这些微结构可能含有与C5b-9结合的细胞膜。
GBM内微结构可能主要起源于足细胞。在这种情况下,C5b-9对足细胞的攻击导致的足细胞和GBM损伤可能部分促成了足细胞内褶和GBM内微结构的形成。