Mannik M, Gauthier V J, Stapleton S A, Agodoa L Y
J Immunol. 1987 Jun 15;138(12):4209-17.
In previously published studies, highly cationized antibodies alone and in immune complexes bound to glomeruli by charge-charge interaction, but only immune complexes persisted in glomeruli. Because normal IgG does not deposit in glomeruli, studies were conducted to determine whether cationized antibodies can be prepared which deposit in glomeruli when bound to antigen but not when free in circulation. A series of cationized rabbit antiHSA was prepared with the number of added amino groups ranging from 13.3 to 60.2 per antibody molecule. Antibodies alone or in preformed soluble immune complexes, prepared at fivefold or 50-fold antigen excess, were administered to mice. With the injection of a fixed dose of 100 micrograms per mouse, antibodies alone did not deposit in glomeruli with less than 29.6 added amino groups by immunofluorescence microscopy. In contrast, 100 micrograms of antibodies with 23.5 added amino groups in immune complexes, made at fivefold antigen excess, formed immune deposits in glomeruli. With selected preparations of cationized, radiolabeled antibodies, deposition in glomeruli was quantified by isolation of mouse glomeruli. These quantitative data were in good agreement with the results of immunofluorescence microscopy. Immune complexes made at 50-fold antigen excess, containing only small-latticed immune complexes with no more than two antibody molecules per complex, deposited in glomeruli similar to antibodies alone. Selected cationized antibodies alone or in immune complexes were administered to mice in varying doses. In these experiments, glomerular deposition of immune complexes, made at fivefold antigen excess, was detected with five- to 10-fold smaller doses than the deposition of the same antibodies alone. These studies demonstrate that antibody molecules in immune complexes are more likely to deposit in glomeruli by charge-charge interactions than antibodies alone.
在先前发表的研究中,高度阳离子化的抗体单独存在时以及与肾小球通过电荷 - 电荷相互作用结合形成免疫复合物时,只有免疫复合物会持续存在于肾小球中。由于正常IgG不会沉积在肾小球中,因此开展了相关研究以确定是否可以制备出这样的阳离子化抗体:当与抗原结合时会沉积在肾小球中,而游离于循环系统中时则不会。制备了一系列阳离子化兔抗人血清白蛋白抗体,每个抗体分子添加的氨基数量范围为13.3至60.2。将单独的抗体或预先形成的可溶性免疫复合物(以抗原过量5倍或50倍制备)注射给小鼠。以每只小鼠固定剂量100微克进行注射,通过免疫荧光显微镜观察,添加氨基少于29.6个的单独抗体不会沉积在肾小球中。相比之下,在抗原过量5倍条件下形成的免疫复合物中,添加了23.5个氨基的100微克抗体在肾小球中形成了免疫沉积物。对于选定的阳离子化、放射性标记抗体制剂,通过分离小鼠肾小球对肾小球中的沉积进行定量。这些定量数据与免疫荧光显微镜观察结果高度一致。在抗原过量50倍条件下形成的免疫复合物,仅包含每个复合物不超过两个抗体分子的小晶格免疫复合物,其在肾小球中的沉积情况与单独抗体相似。将选定的阳离子化抗体单独或与免疫复合物以不同剂量注射给小鼠。在这些实验中,与单独注射相同抗体相比,在抗原过量5倍条件下形成的免疫复合物以小5至10倍的剂量就能检测到肾小球沉积。这些研究表明,免疫复合物中的抗体分子比单独的抗体更有可能通过电荷 - 电荷相互作用沉积在肾小球中。