Agodoa L Y, Gauthier V J, Mannik M
J Exp Med. 1983 Oct 1;158(4):1259-71. doi: 10.1084/jem.158.4.1259.
This study was conducted to determine whether multivalent, precipitating antigens are required for formation of subepithelial electron-dense immune deposits in glomeruli. 2-nitro-4-azidophenyl (NAP) was conjugated with variable density to human serum albumin (HSA) to yield nonprecipitating (NAP3.1 X HSA and NAP11.4 X HSA) and precipitating (NAP19.7 X HSA) antigens with antibodies to the hapten. These antigen preparations were cationized with ethylene diamine to enhance deposition in renal glomeruli due to interaction with the fixed negative charges in the glomerular capillary wall. Following injection into the left renal artery of rats these antigens alone persisted in the glomeruli for a relatively short time by immunofluorescence microscopy. When antibodies to NAP were injected intravenously after the antigen injection, the nonprecipitating antigens and antibodies were detectable in the glomeruli by immunofluorescence microscopy up to 8 h, comparable to antigen alone. Electron-dense deposits were not formed in these glomeruli. In contrast, when the precipitating antigen was injected and followed by antibodies to the hapten, antigen and antibody were detected by immunofluorescence microscopy through 96 h. In these specimens electron-dense deposits were present from 40 min through 96 h and after 24 h the deposits were present only in the subepithelial area. The same results were obtained when the nonprecipitating hapten-carrier conjugates were followed with antibodies to the carrier molecule. These data indicate that the persistence of immune deposits by immunofluorescence microscopy and the formation of electron-dense deposits in the subepithelial area require a precipitating antigen-antibody system.
本研究旨在确定肾小球上皮下电子致密免疫沉积物的形成是否需要多价沉淀抗原。将2-硝基-4-叠氮苯基(NAP)以可变密度与人血清白蛋白(HSA)偶联,以产生与半抗原抗体结合的非沉淀性(NAP3.1×HSA和NAP11.4×HSA)和沉淀性(NAP19.7×HSA)抗原。这些抗原制剂用乙二胺阳离子化,以增强其在肾小球中的沉积,这是由于与肾小球毛细血管壁上的固定负电荷相互作用。将这些抗原单独注入大鼠左肾动脉后,通过免疫荧光显微镜观察,它们在肾小球中持续的时间相对较短。在注入抗原后静脉注射抗NAP抗体,通过免疫荧光显微镜在肾小球中可检测到非沉淀性抗原和抗体长达8小时,与单独的抗原相当。这些肾小球中未形成电子致密沉积物。相比之下,当注入沉淀性抗原并随后注入半抗原抗体时,通过免疫荧光显微镜在96小时内均可检测到抗原和抗体。在这些标本中,从40分钟到96小时均存在电子致密沉积物,24小时后沉积物仅存在于上皮下区域。当用载体分子抗体追踪非沉淀性半抗原-载体偶联物时,也得到了相同的结果。这些数据表明,通过免疫荧光显微镜观察到的免疫沉积物的持续存在以及上皮下区域电子致密沉积物的形成需要沉淀性抗原-抗体系统。