Pure anti-dsDNA mAbs need chromatin structures to promote glomerular mesangial deposits in BALB/c mice

Pure anti-dsDNA mAbs need chromatin structures to promote glomerular mesangial deposits in BALB/c mice
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DOI:
10.3109/08916930903305633
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发表时间:
2010-03-01
期刊:
影响因子:
3.5
通讯作者:
Rekvig, Ole Petter
Rekvig, Ole Petter
中科院分区:
医学4区
文献类型:
--
作者:
Fenton, Kristin Andreassen;Tommeras, Berit;Rekvig, Ole Petter

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致肾炎抗体的肾小球靶点已被确定为膜相关染色质片段。人们对它们沉积的过程知之甚少。为了确定抗体介导的肾炎的早期事件,我们将高纯度的抗 dsDNA mAb 注射到 BALB/c 小鼠体内。接受一剂抗 dsDNA mAb 的小鼠在 6 或 24 小时后被处死。免疫电子显微镜未观察到单克隆抗体与肾小球膜或系膜基质的直接结合。相反,在 4 周内重复注射相同的抗体导致电子致密结构主要沉积在系膜基质中。通过共定位免疫电子显微镜测定,这些结构含有单克隆抗体和染色质片段。生物素化抗 dsDNA mAb,注入肾病 (NZB x NZW)F1 或 MRL
The glomerular targets for nephritogenic antibodies have been identified as membrane-associated chromatin fragments. The processes responsible for their deposition are poorly understood. To determine early events in antibody-mediated nephritis, we injected highly pure anti-dsDNA mAbs into BALB/c mice. Mice receiving one dose of anti-dsDNA mAbs were sacrificed 6 or 24 h later. No direct binding of mAbs to glomerular membranes or to the mesangial matrix was observed by immune electron microscopy. In contrast, repeated injections of the same antibodies over 4 weeks resulted in deposition of electron dense structures predominantly in the mesangial matrix. These structures contained mAbs and chromatin fragments as determined by co-localization immune electron microscopy. Biotinylated anti-dsDNA mAbs, injected into nephritic (NZB x NZW)F1 or MRL