FEATURES OF SYSTEMIC LUPUS-ERYTHEMATOSUS IN MICE INJECTED WITH BACTERIAL LIPOPOLYSACCHARIDES - IDENTIFICATION OF CIRCULATING DNA AND RENAL LOCALIZATION OF DNA-ANTI-DNA COMPLEXES
FEATURES OF SYSTEMIC LUPUS-ERYTHEMATOSUS IN MICE INJECTED WITH BACTERIAL LIPOPOLYSACCHARIDES - IDENTIFICATION OF CIRCULATING DNA AND RENAL LOCALIZATION OF DNA-ANTI-DNA COMPLEXES
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DOI：
10.1084/jem.145.5.1115
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发表时间：
1977-01-01
影响因子：
15.3
通讯作者：
MIESCHER, PA
中科院分区：
文献类型：
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作者：
IZUI, S;LAMBERT, PH;MIESCHER, PA
在注射[鼠伤寒沙门氏菌，S。大肠杆菌或大肠杆菌]脂多糖（LPS）在小鼠中的作用，首先是DNA释放到血浆中，其次是诱导抗DNA抗体。从血浆中纯化循环DNA并进行物理免疫化学表征。这种DNA的密度与哺乳动物细胞DNA相似，大小为4-6S，可能是单链DNA（SSDNA）和双链DNA（DSDNA）的混合物，或具有一些单链区域的DSDNA。这种纯化的DNA与抗DNA抗体反应，该抗体早在小鼠单次注射LPS后3天就出现了。在血清中，未检测到DNA-抗DNA复合物，尽管在注射LPS后5-8天证实了未鉴定的循环免疫复合物样物质。在组织中，特别是在肾小球，细颗粒免疫复合物型免疫球蛋白沉积出现沿着肾小球毛细血管壁和系膜注射LPS后3天。抗DNA抗体的水平与肾小球沉积物的强度之间存在直接相关性，并且从肾脏洗脱的免疫球蛋白中约40%是抗DNA抗体，这表明位于肾脏中的一些免疫复合物是DNA-抗DNA复合物。提出了小鼠注射LPS后DNA-抗DNA复合物肾小球定位的假设机制。首先，DNA，这是在注射LPS后释放到循环血液中，可能会结合到肾小球，可能是在肾小球基底膜（GBM），通过GBM对DNA的高亲和力;其次，循环中的抗DNA抗体，出现后，可能会与肾小球结合的DNA反应，形成免疫复合物独立于循环免疫复合物。不排除免疫复合物直接沉积的可能性。
After injection of [Salmonella typhimurium, S. enteritidis or Escherichia coli] lipopolysaccharides (LPS) in mice, there is first a release of DNA into plasma and secondly an induction of anti-DNA antibodies. The circulating DNA was purified from plasma and physico-immunochemically characterized. This DNA has a similar density to mammalian cellular DNA, is 4-6S in size, and probably represents a mixture of single-stranded DNA (SSDNA) and double-stranded DNA (DSDNA), or DSDNA with some single-stranded regions. This purified DNA reacts with anti-DNA antibodies which appeared as early as 3 days after a single injection of LPS in mice. In serum, DNA-anti-DNA complexes were not detected, although unidentified circulating immune complex-like material was demonstrated 5-8 days after the injection of LPS. In tissues, particularly in renal glomeruli, fine granular immune complex-type immunoglobulin deposits appeared along the glomerular capillary walls and in the mesangium 3 days after the injection of LPS. There is a direct correlation between the level of anti-DNA antibodies and the intensity of glomerular deposits, and about 40% of immunoglobulins eluted from kidneys are anti-DNA antibodies, indicating that some of the immune complexes localized in kidneys are DNA-anti-DNA complexes. The following hypothetical mechanism for the glomerular localization of DNA-anti-DNA complexes after the injection of LPS in mice in proposed. First, DNA, which was released in circulating blood after injection of LPS, might bind to renal glomeruli, probably on glomerular basement membranes (GBM), through a high affinity of GBM for DNA; secondly, circulating anti-DNA antibodies, which appear later, might react with the glomerular-bound DNA and form immune complexes independently of circulating immune complexes. The possibility of direct deposition of immune complexes is not eliminated.