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肾小球基底膜和胶原蛋白对DNA的特殊亲和力的体外证明。系统性红斑狼疮中DNA-抗DNA复合物局部形成的一种可能基础。

In vitro demonstration of a particular affinity of glomerular basement membrane and collagen for DNA. A possible basis for a local formation of DNA-anti-DNA complexes in systemic lupus erythematosus.

作者信息

Izui S, Lambert P H, Miescher P A

出版信息

J Exp Med. 1976 Aug 1;144(2):428-43. doi: 10.1084/jem.144.2.428.

Abstract

In vitro, collagen and collagen-like material in GBM, were demonstrated to have a particular high affinity for any DNA tested (mammalian, bacterial, viral, and plant). GBM fixed DNA 40-80 times more than HGG and BSA and 10-40 times more than bacterial LPS. GBM has a higher affinity for SSDNA than for DSDNA. This binding was inhibited at low pH, low ionic strength, and in the presence of anionic detergents, indicating that the highly negatively charged DNA may interact with the basic site on collagen or GBM by electrostatic forces. This interaction was competitively interfered with by DNA-binding proteins such as Clq. Complexes formed of DNA and anti-DNA antibodies did not exhibit the same binding property as free DNA. However, DNA which was already bound to GBM or to collagen could very efficiently bind anti-DNA antibodies and form immune complexes which would remain on these structures. The biological significance of the binding of DNA to GBM or to collagen should be particularly considered in relation to the pathogenesis of SLE. It is possible that DNA released from disrupted or degenerating cells would bind to surrounding collagen fibers or to basement membranes and then act as an immunoabsorbant for circulating anti-DNA antibodies. Some evidence for an in vivo binding of SSDNA to renal structures was obtained in mice treated with bacterial LPS 2 days before the injection of SSDNA.

摘要

在体外实验中,已证明肾小球基底膜(GBM)中的胶原蛋白和类胶原蛋白材料对任何测试的DNA(哺乳动物、细菌、病毒和植物来源的DNA)都具有特别高的亲和力。GBM固定DNA的能力比高分级胶质瘤(HGG)和牛血清白蛋白(BSA)高40 - 80倍,比细菌脂多糖(LPS)高10 - 40倍。GBM对单链DNA(SSDNA)的亲和力高于双链DNA(DSDNA)。这种结合在低pH值、低离子强度以及存在阴离子去污剂的情况下会受到抑制,这表明高度带负电荷的DNA可能通过静电力与胶原蛋白或GBM上的碱性位点相互作用。这种相互作用会受到诸如Clq等DNA结合蛋白的竞争性干扰。由DNA和抗DNA抗体形成的复合物不具有与游离DNA相同的结合特性。然而,已经与GBM或胶原蛋白结合的DNA能够非常有效地结合抗DNA抗体并形成免疫复合物,这些复合物会保留在这些结构上。DNA与GBM或胶原蛋白结合的生物学意义在系统性红斑狼疮(SLE)的发病机制方面应特别予以考虑。从受损或退化细胞释放的DNA可能会与周围的胶原纤维或基底膜结合,然后作为循环抗DNA抗体的免疫吸附剂发挥作用。在用细菌LPS处理小鼠2天后注射SSDNA,获得了一些关于SSDNA在体内与肾脏结构结合的证据。

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