Wedeen R P, Batuman V, Sobel H
Nephron. 1981;29(5-6):258-64. doi: 10.1159/000182385.
The effect of antiproximal tubule basement membrane (TBM) and brush border (BB) antibodies on p-aminohippurate (PAH) transport was evaluated in a rat model of immunologically mediated interstitial nephritis. Immunized rats developed anti-TBM antibody titers ranging from 1 to 3,072 with continuous linear IgG and interrupted C3 deposits in the TBM. Circulating anti-BB antibodies were detected in half of the immunized rats in titers ranging from 1 to 128. Heavy IgG deposition was present in the BB when circulating anti-BB antibody titers exceeded eight and proteinuria was present. When anti-TBM antibody titers were 1,024 or greater the slice-to-medium PAH concentration ratio (S/M) was significantly reduced (p less than 0.001). Combined immunofluorescent microscopy and section freeze-dry autoradiography revealed normal cellular distribution of PAH-3H in all proximal tubules except in rat microscopic foci of interstitial nephritis in which concentrative transport was absent. However, luminal secretion of PAH-3H was strikingly reduced in tubules with heavy IgG BB deposits. 3-hour PAH secretion in vivo fell significantly in rats with circulating and tissue anti-BB antibodies. Antibody inhibition of PAH transport appeared to be independent of morphologic damage.
Anti-TBM antibodies were associated with decreased slice uptake of PAH-3H while anti-BB antibodies were associated with decreased luminal PAH secretion in vitro and in vivo.
在免疫介导的间质性肾炎大鼠模型中,评估了抗近端肾小管基底膜(TBM)和刷状缘(BB)抗体对对氨基马尿酸(PAH)转运的影响。免疫大鼠产生的抗TBM抗体滴度范围为1至3,072,TBM中IgG呈连续线性沉积且C3呈间断沉积。在一半的免疫大鼠中检测到循环抗BB抗体,滴度范围为1至128。当循环抗BB抗体滴度超过8且出现蛋白尿时,BB中有大量IgG沉积。当抗TBM抗体滴度为1,024或更高时,切片与介质中PAH浓度比(S/M)显著降低(p<0.001)。联合免疫荧光显微镜检查和切片冷冻干燥放射自显影显示,除了间质性肾炎大鼠微观病灶中缺乏浓缩转运外,所有近端小管中PAH-3H的细胞分布均正常。然而,在有大量IgG BB沉积的小管中,PAH-3H的管腔分泌显著减少。在具有循环和组织抗BB抗体的大鼠中,体内3小时PAH分泌显著下降。抗体对PAH转运的抑制作用似乎与形态学损伤无关。
抗TBM抗体与PAH-3H切片摄取减少有关,而抗BB抗体与体外和体内管腔PAH分泌减少有关。