Nagata M, Akioka Y, Tsunoda Y, Komatsu Y, Kawaguchi H, Yamaguchi Y, Ito K
Department of Pediatric Nephrology, Tokyo Women's Medical College, Japan.
Kidney Int. 1995 Aug;48(2):527-35. doi: 10.1038/ki.1995.323.
The role of glomerular macrophages in IgA nephropathy in children was investigated using a new monoclonal antibody (KP1) as a probe. The average number of glomerular macrophages per patient (ANM/P) was closely correlated with the degree of hematuria (P < 0.01) as well as with the degree of leukocyturia (P < 0.01) in the absence of any correlation with proteinuria, serum IgA levels or the interval between the detection of urine abnormalities and renal biopsy. ANM/P was significantly higher in patients diagnosed pathologically as having focal and diffuse proliferative glomerulonephritis than in patients with minor glomerular abnormalities or advanced sclerosis (P < 0.05). Among various types of glomerular morphology in individual patients, macrophages predominantly infiltrated glomeruli with cell-proliferative lesions despite an absence of any increase in glomeruli with minor abnormalities or with sclerosis. Macrophages were mainly localized within the capillary lumen in association with endocapillary proliferative lesions (tuft necrosis), they accumulated in areas of mesangial proliferation, and they were attached to Bowman's capsule in segmental lesions. Macrophages were less evident in sclerosis. Furthermore, ultrastructural analysis revealed macrophages in the paramesangial areas in close proximity to lytic changes in the glomerular basement membrane and effacement of epithelial foot processes. In addition, some cases in repeat biopsy shows prolonged or increased values of ANM/P after several years of interval in association with progression of proliferative lesions. These results suggest that macrophages infiltrate glomeruli during acute glomerular inflammation, and that they are involved in mesangial proliferation or the development of extracapillary lesions in the absence of apparent clinical symptoms. Furthermore, recurrence or prolonged infiltration may promote progression of IgA nephropathy.
使用一种新型单克隆抗体(KP1)作为探针,研究了肾小球巨噬细胞在儿童IgA肾病中的作用。每位患者的肾小球巨噬细胞平均数量(ANM/P)与血尿程度密切相关(P < 0.01),也与白细胞尿程度密切相关(P < 0.01),而与蛋白尿、血清IgA水平或尿液异常检测与肾活检之间的间隔时间无关。病理诊断为局灶性和弥漫性增殖性肾小球肾炎的患者的ANM/P显著高于肾小球轻度异常或晚期硬化患者(P < 0.05)。在个体患者的各种肾小球形态类型中,巨噬细胞主要浸润有细胞增殖性病变的肾小球,尽管轻度异常或硬化的肾小球没有任何增加。巨噬细胞主要定位于毛细血管腔内,与毛细血管内增生性病变(肾小球丛坏死)相关,它们在系膜增生区域积聚,并在节段性病变中附着于鲍曼囊。在硬化区域巨噬细胞不太明显。此外,超微结构分析显示,在肾小球系膜旁区域存在巨噬细胞,它们紧邻肾小球基底膜的溶解变化和上皮足突的消失。此外,一些重复活检的病例显示,在数年间隔后,随着增殖性病变的进展,ANM/P值延长或增加。这些结果表明,巨噬细胞在急性肾小球炎症期间浸润肾小球,并且在没有明显临床症状的情况下参与系膜增生或毛细血管外病变的发展。此外,复发或长期浸润可能促进IgA肾病的进展。