Quantitative studies of in situ immune complex glomerulonephritis in the rat induced by planted, cationized antigen.
Quantitative studies of in situ immune complex glomerulonephritis in the rat induced by planted, cationized antigen.
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DOI：
10.1084/jem.155.2.460
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发表时间：
1982-02-01
期刊：
影响因子：
--
通讯作者：
Vogt A
中科院分区：
文献类型：
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作者：
Oite T;Batsford SR;Mihatsch MJ;Takamiya H;Vogt A
阳离子化人IgG可与大鼠肾小球基底膜（GBM）结合，作为种植抗原，诱导原位免疫复合物形成，并伴有严重的肾小球肾炎。通过左肾动脉灌注高度阳离子化的人IgG（等电点大于9.5）导致优先定位在灌注的肾脏内（高达注射剂量的56%）;静脉给药后，只有4%与肾脏结合。植入的抗原定位于沿着肾小球毛细血管壁，并且在灌注后1小时静脉内施用的抗体可接近，此时几乎没有抗原残留在循环中。与抗体复合时，阳离子化人IgG在灌注肾中的持续时间显着延长; 12 d后仍有一半的阳离子化人IgG存在。抗原和抗体的消失率存在差异，因为阳离子化的人IgG比抗体更快地从肾脏中去除，抗体的结合在第一周期间几乎保持不变。肾灌注至少20 μg阳离子化人IgG，然后静脉注射抗体，定期诱导严重肾小球肾炎，蛋白尿至少100 mg/24 h。所诱导的蛋白尿的程度和持续时间依赖于灌注的阳离子化人IgG的剂量。使用放射性标记的抗原和抗体的实验表明，在肾灌注20 μg阳离子化人IgG后，在注射抗体时有11.1 μg与肾结合。在蛋白尿发作时，灌注肾中存在4.0 μg抗原和31.9 μg抗人IgG抗体。免疫荧光显示沿着GBM的阳离子化人IgG和兔IgG（抗人IgG）组成的免疫沉积物。染色模式是线性（融合）在第一个2天，并成为颗粒在病程中。电子显微镜下，一个突出的发现是致密沉积物的积聚，主要在上皮下空间和裂隙孔下方。
Cationized human IgG can bind to the rat glomerular basement membrane (GBM), act as planted antigen, and induce in situ immune complex formation accompanied by severe glomerulonephritis. Perfusion of highly cationized human IgG (isoelectric point {more than} 9.5) via the left renal artery resulted in preferential localization within the perfused kidney (up to 56 percent of dose injected); after intravenous administration, only 4 percent was bound to the kidneys. The planted antigen was localized along the glomerular capillary walls and was accessible for antibody administered intravenously 1 h after perfusion, when virtually no antigen remained in the circulation. Persistence of cationized human IgG in the perfused kidney was markedly prolonged when complexed with antibody; one-half the cationized human IgG was still present after 12 d. There was a difference in the disappearance rates of antigen and antibody, as cationized human IgG was removed faster from the kidney than the antibody, the binding of which remained almost unchanged during the first week. Renal perfusion of a minimum of 20 μg of cationized human IgG, followed by intravenous injection of antibody, regularly induced severe glomerulonephritis with a proteinuria of at least 100 mg/24 h. The degree and the persistence of proteinuria induced depended on the dose of cationized human IgG perfused. Experiments using radiolabeled antigen and antibody showed that after renal perfusion of 20 μg cationized human IgG, 11.1 μg was kidney bound at the time of antibody injection. At the onset of proteinuria, 4.0 μg of antigen and 31.9 μg of anti-human IgG antibody were present in the perfused kidney. Immunofluorescence revealed immune deposits consisting of cationized human IgG and rabbit IgG (anti-human IgG) along the GBM. The staining pattern was linear (confluent) during the first 2 d and became granular during the course of the disease. Electronmicroscopically, a prominent finding was the accumulation of dense deposits, mainly in the subepithelial space and beneath the slit pores.