Cosio F G, Bakaletz A P
Department of Medicine, Ohio State University, Columbus 43210.
J Clin Invest. 1987 Nov;80(5):1270-9. doi: 10.1172/JCI113202.
In the present study, we have evaluated how plasma fibronectin (FN) and tissue FN can affect the clearance from the circulation and organ uptake of antigen or immune complexes (IC) that have the capacity to bind to FN. Phenylated gelatin (DNP-GL) (a FN binding antigen) and IC composed of DNP-GL and monoclonal IgGl anti-dinitrophenol (DNP) antibodies were tested. These probes were compared with DNP-bovine serum albumin (BSA) (a non-FN-binding antigen) and DNP-BSA IC formed with the same anti-DNP antibody used for the preparation of DNP-GL IC. We found evidence that DNP-GL, but not DNP-BSA, formed complexes with soluble FN in vitro and the data strongly suggest that DNP-GL-FN complexes form in vivo. The formation of complexes with plasma FN aided in the clearance of DNP-GL from the circulation, as shown by the facts that DNP-GL was removed from the circulation much faster than DNP-BSA and that complexes of DNP-GL with plasma FN were removed from the circulation faster than uncomplexed DNP-GL. The sites of deposition of DNP-GL were also different from those of DNP-BSA. Thus, DNP-GL demonstrated higher hepatic, splenic, and renal uptake than did DNP-BSA. Renal uptake of DNP-GL was quite high despite the fact that DNP-GL is anionic. Indeed, expressed per gram of tissue, liver and kidney deposition of DNP-GL was not significantly different. By immunofluorescence microscopy, DNP-GL could be demonstrated in hepatic sinusoids and glomerular mesangium. In vitro, DNP-GL bound to FN in the mesangium of frozen sections of kidney tissue. IC formed with DNP-GL or DNP-BSA demonstrated virtually the same size, yet the fate of DNP-GL IC was strikingly different from that of DNP-BSA IC. The removal of DNP-GL IC from the circulation was mediated by the antigen and not by Fc receptors since gelatin (an inhibitor of DNP-GL clearance) but not aggregated IgG (an inhibitor of Fc receptors) inhibited the removal of DNP-GL IC from the circulation. In summary, these studies suggest that the ability of an antigen or IC to bind to FN markedly influences the fate of that antigen or IC. Specifically, binding to FN accelerates clearance from the circulation and favors hepatic and renal (primarily mesangial) uptake of the FN binding antigen of IC.
在本研究中，我们评估了血浆纤连蛋白（FN）和组织FN如何影响具有与FN结合能力的抗原或免疫复合物（IC）从循环中的清除以及器官摄取。测试了苯基化明胶（DNP-GL）（一种FN结合抗原）以及由DNP-GL和单克隆IgG1抗二硝基苯酚（DNP）抗体组成的IC。将这些探针与DNP-牛血清白蛋白（BSA）（一种非FN结合抗原）以及用制备DNP-GL IC所用的相同抗DNP抗体形成的DNP-BSA IC进行比较。我们发现有证据表明，DNP-GL而非DNP-BSA在体外与可溶性FN形成复合物，并且数据强烈表明DNP-GL-FN复合物在体内形成。与血浆FN形成复合物有助于DNP-GL从循环中清除，这表现为以下事实：DNP-GL从循环中清除的速度比DNP-BSA快得多，并且DNP-GL与血浆FN的复合物从循环中清除的速度比未复合的DNP-GL快。DNP-GL的沉积部位也与DNP-BSA不同。因此，DNP-GL在肝脏、脾脏和肾脏中的摄取高于DNP-BSA。尽管DNP-GL是阴离子性的，但其在肾脏中的摄取仍然相当高。实际上，以每克组织计算，DNP-GL在肝脏和肾脏中的沉积并无显著差异。通过免疫荧光显微镜检查，可在肝血窦和肾小球系膜中检测到DNP-GL。在体外，DNP-GL可与肾组织冰冻切片的系膜中的FN结合。由DNP-GL或DNP-BSA形成的IC大小几乎相同，但DNP-GL IC的命运与DNP-BSA IC明显不同。DNP-GL IC从循环中的清除是由抗原介导的，而非Fc受体，因为明胶（DNP-GL清除的抑制剂）而非聚集的IgG（Fc受体的抑制剂）抑制了DNP-GL IC从循环中的清除。总之，这些研究表明抗原或IC与FN结合的能力显著影响该抗原或IC的命运。具体而言，与FN结合可加速从循环中的清除，并有利于肝脏和肾脏（主要是系膜）摄取与FN结合的抗原或IC。
