Cosio F G, Bakaletz A P, Mahan J D
Department of Internal Medicine, Ohio State University, Columbus.
Kidney Int. 1990 Jun;37(6):1429-37. doi: 10.1038/ki.1990.133.
The present study compared directly the ability of precipitating and nonprecipitating antibodies to form and sustain glomerular immune deposits. The antigen phenylated gelatin (DNP-GL) was injected i.v. into rats. DNP-GL is cleared from the circulation rapidly and becomes localized in glomeruli. Two hours later, rats received either precipitating or nonprecipitating mouse monoclonal anti-DNP antibodies. These antibodies were comparable with respect to size, affinity, number of antigen combining sites and isoelectric point. However, in vitro, nonprecipitating antibodies demonstrated a faster dissociation rate from antigen than precipitating antibodies. Control rats received DNP-GL alone or antibody alone. Antibody deposition in glomeruli was quantitated by Computerized Image Analysis (CIA) of immunoperoxidase stained tissue sections and by glomerular radioactive counts in experiments using 125I labelled antibodies. We demonstrated that glomerular uptake of anti-DNP antibody was similar two hours after injection of precipitating and nonprecipitating antibodies. However, six or more hours after injection, significantly less antibody was present in the glomeruli of rats injected with nonprecipitating antibodies. These differences could not be explained by a greater rate of antigen removal from kidney in rats injected with nonprecipitating antibodies. To assess whether nonprecipitating antibodies modify the glomerular binding and retention of precipitating antibody, in a separate series of experiments rats were injected with equal amounts of precipitating and nonprecipitating antibodies. Both types of antibody bound to glomeruli. However, with time glomerular antibody levels paralleled those found in rats injected with nonprecipitating antibody alone. We conclude that the precipitating characteristics of antibodies do not affect their ability to deposit in kidney.(ABSTRACT TRUNCATED AT 250 WORDS)
本研究直接比较了沉淀性抗体和非沉淀性抗体形成并维持肾小球免疫沉积物的能力。将抗原苯化明胶(DNP-GL)静脉注射到大鼠体内。DNP-GL迅速从循环中清除并定位于肾小球。两小时后,给大鼠注射沉淀性或非沉淀性小鼠单克隆抗DNP抗体。这些抗体在大小、亲和力、抗原结合位点数量和等电点方面具有可比性。然而,在体外,非沉淀性抗体与抗原的解离速度比沉淀性抗体更快。对照大鼠单独接受DNP-GL或单独接受抗体。通过对免疫过氧化物酶染色组织切片进行计算机图像分析(CIA)以及在使用125I标记抗体的实验中通过肾小球放射性计数来定量肾小球中的抗体沉积。我们证明,在注射沉淀性和非沉淀性抗体两小时后,肾小球对抗DNP抗体的摄取相似。然而,注射后六小时或更长时间,注射非沉淀性抗体的大鼠肾小球中存在的抗体明显较少。这些差异不能用注射非沉淀性抗体的大鼠肾脏中抗原清除率更高来解释。为了评估非沉淀性抗体是否会改变沉淀性抗体在肾小球的结合和滞留,在另一系列实验中,给大鼠注射等量的沉淀性和非沉淀性抗体。两种类型的抗体都与肾小球结合。然而,随着时间的推移,肾小球抗体水平与单独注射非沉淀性抗体的大鼠中发现的水平相似。我们得出结论,抗体的沉淀特性不影响其在肾脏中的沉积能力。(摘要截选至250字)