Proteinuria and structural alterations in rat glomerular basement membranes induced by intravenously injected anti-laminin immunoglobulin G

Proteinuria and structural alterations in rat glomerular basement membranes induced by intravenously injected anti-laminin immunoglobulin G
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静脉注射抗层粘连蛋白G引起的大鼠肾小球基底膜蛋白尿及结构改变

DOI:
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发表时间:
1982
影响因子:
15.3
通讯作者:
J. Caulfield
J. Caulfield
中科院分区:
医学1区
文献类型:
--
作者:
D. Abrahamson;J. Caulfield

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层粘连蛋白是一种确定的基底膜糖蛋白,在绵羊中产生针对层粘连蛋白的抗体,并通过层粘连蛋白-琼脂糖凝胶(S α L)上的免疫吸附进行亲和纯化。当静脉注射到大鼠中时,S α L以线性模式迅速结合到所有肾小球的外周和系膜区的肾小球基底膜(GBM),并且当注射大于0.5 mg S α L时,也结合到一些管状BM。1-2在注射辣根过氧化物酶(HRP)和S α L的缀合物后h,HRP反应产物存在于整个GBM和系膜基质的整个厚度中。在40-950 μ g IgG剂量范围内,[125 I]S α L与肾脏的体内结合呈线性增加,约占注射剂量/g肾脏的2%。当注射4 mg [125 I]S α L时,结合率为1.5%或62 μ g/g肾脏。注射0.5-1.6 mg S α L的大鼠在注射后7周内未出现蛋白尿。相反,所有接受4 mg S α L注射的动物在3-6周内逐渐变成蛋白尿。在这些动物的GBM中观察到增厚、重复和絮状内皮下沉积物。此外,单核细胞粘附于GBM并浸润到内皮下方。然而,很少观察到大鼠C3的沉积,并且在接受S α L的任何大鼠的肾小球中均未观察到大鼠IgG。注射后10 wk,系膜内S α L的表达量明显高于周围GBM。这些结果表明,S α L与GBM的相互作用,可能与浸润的单核细胞一致,逐渐改变了肾小球的结构和渗透性特征,而不依赖于宿主抗S α L体液应答。
Antibodies against laminin, which is a defined glycoprotein of basement membranes, were produced in sheep and affinity purified by immunoadsorption on laminin-Sepharose (S alpha L). When injected intravenously into rats, S alpha L rapidly bound in a linear pattern to the glomerular basement membrane (GBM) in the peripheral and mesangial regions of all glomeruli, and, when greater than 0.5 mg S alpha L was injected, to some tubular BM as well. 1-2 h after the injection of conjugates of horseradish peroxidase (HRP) and S alpha L, HRP reaction product was present throughout the full thickness of the GBM and mesangial matrix. [125I]S alpha L binding to the kidney in vivo increased linearly over the dose range of 40-950 micrograms of IgG and accounted for approximately 2% of the injected dose/g kidney. When 4 mg of [125I]S alpha L was injected, 1.5% or 62 micrograms/g kidney was bound. Proteinuria did not develop within 7 wk of injection in rats that received 0.5-1.6 mg of S alpha L. In contrast, all animals that received injections of 4 mg of S alpha L gradually became proteinuric within 3-6 wk. Thickening, reduplication, and flocculent subendothelial deposits were observed in the GBM of these animals. In addition, mononuclear cells adhered to the GBM and infiltrated beneath the endothelium. However, the deposition of rat C3 was infrequently observed, and rat IgG was not seen in the glomeruli of any rat that received S alpha L. 10 wk after injection, much greater amounts of S alpha L appeared within the mesangium than the peripheral GBM. These results demonstrate that the interaction of S alpha L with the GBM, possibly in concert with infiltrating mononuclear cells, gradually altered the structure and permeability characteristics of the glomerulus independent of a host anti-S alpha L humoral response.
DOI: 10.1172/jci110304
发表时间: 1981-01-01
影响因子: 15.9
作者:
HOLDSWORTH, SR;NEALE, TJ;WILSON, CB
通讯作者: WILSON, CB
啮齿动物组织中巢蛋白(一种硫酸化基底膜成分)的免疫定位,并与 GP-2(层粘连蛋白)进行比较。
DOI: --
发表时间: 1981
期刊: The American journal of pathology
影响因子: --
作者:
Bender,BL;Jaffe,R;Carlin,B;Chung,AE
通讯作者: Chung,AE