Increased expression of monocyte chemoattractant protein-1 in anti-thymocyte antibody-induced glomerulonephritis.
Increased expression of monocyte chemoattractant protein-1 in anti-thymocyte antibody-induced glomerulonephritis.
复制标题
抗胸腺细胞抗体诱导的肾小球肾炎中单核细胞趋化蛋白-1 表达增加。
DOI：
10.1038/ki.1993.346
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发表时间：
1993
影响因子：
19.6
通讯作者：
Schlöndorff,D
中科院分区：
文献类型：
--
作者：
Stahl,RA;Thaiss,F;Disser,M;Helmchen,U;Hora,K;Schlöndorff,D
抗胸腺细胞抗体诱导的肾小球肾炎中单核细胞趋化蛋白-1的表达增加。肾小球内单核-巨噬细胞浸润是肾小球肾炎的标志之一，可能在其发病中起重要作用。单核细胞趋化蛋白-1（MCP-1）和集落刺激因子-1（CSF-1）是单核细胞特异性的细胞因子，具有单核细胞趋化和激活活性。MCP-1和CSF-1可以由包括肾小球系膜细胞在内的几种细胞类型产生，并且可以被细胞因子和免疫复合物刺激。应用北方印迹法和免疫组化方法研究了增生性肾小球肾炎模型中CSF-1和MCP-1的表达。通过静脉注射针对位于肾小球系膜细胞上的抗原的异源抗胸腺细胞抗血清（ATS）在大鼠中诱导肾小球病变。北方印迹分析显示，从对照未处理大鼠和从注射ATS抗体30分钟至3周后的大鼠分离的肾小球中CSF-1的量相当。在对照肾小球中，未检测到MCP-1的mRNA水平，但在肾炎诱导后30分钟显著增加，然后在24小时减少，并在疾病诱导后5天和21天再次增加。注射ATS后30分钟或24小时MCP-1 mRNA水平的增加，如果大鼠被眼镜蛇毒注射耗尽补体，则显着减弱。抗体注射后的这些时间点与系膜免疫复合物形成（30分钟），系膜溶解（24小时）和增生性肾小球肾炎（5和21天）。通过免疫组织学，MCP-1的存在被证明在肾小球中具有主要的系膜分布。MCP-1的系膜免疫荧光遵循与疾病过程诱导后MCP-1的mRNA相似的模式，即，其在30分钟后增加，24小时后减少，并且在3周时再次增加。在抗体注射的30分钟内，在肾小球中观察到单核细胞-巨噬细胞浸润增加，其维持至诱导肾小球肾炎的三周。在注射ATS前用眼镜蛇毒因子去分解大鼠，肾小球内MCP-1的表达仍较低，未出现单核/巨噬细胞内流。我们的结论是MCP-1增加早期在肾小球免疫介导的系膜增生性肾小球肾炎大鼠。这种增加是由继发于肾小球系膜处原位免疫复合物形成的补体激活介导的。MCP-1的升高可能在单核/巨噬细胞进入肾小球的募集中起重要作用，随后原位免疫复合物形成。
Increased expression of monocyte chemoattractant protein-1 in anti-thymocyte antibody-induced glomerulonephritis. The infiltration of monocytes-macrophages in the glomerulus is one of the hallmarks of glomerulonephritis and may play an important pathogenetic role. Monocyte chemoattractant protein-1 (MCP-1) and colony stimulating factor-1 (CSF-1) are monocyte-specific cytokines with chemoattractant and activating activities for monocytes. MCP-1 and CSF-1 can be generated by several cell types, including glomerular mesangial cells, and can be stimulated by cytokines and immune complexes. To study the expression of CSF-1 and MCP-1 in a model of proliferative glomerulonephritis we used Northern blot analysis and immuno-histochemistry. The glomerular lesion was induced in rats by the i.v. injection of a heterologous anti-thymocyte antiserum (ATS), directed against an antigen which is localized on glomerular mesangial cells. Northern blot analysis revealed comparable amounts of CSF-1 in glomeruli isolated from control untreated rats, and from rats after 30 minutes to three weeks of injection of ATS antibody. In control glomeruli no mRNA levels for MCP-1 were detectable, but increased markedly 30 minutes after the induction of the nephritis, were then reduced at 24 hours and increased again at 5 and 21 days after induction of the disease. The increase in mRNA levels for MCP-1 30 minutes or 24 hours after ATS injection was markedly attenuated if rats were complement depleted by cobra venom injection. These time points following antibody injection were associated with mesangial immune complex formation (30 min), mesangiolysis (24 hr) and proliferative glomerulonephritis (5 and 21 days). By immunohistology the presence of MCP-1 was demonstrated in glomeruli with a predominant mesangial distribution. The mesangial immunofluorescence for MCP-1 followed a pattern similar to that of the mRNA for MCP-1 after induction of the disease process, that is, it increased after 30 minutes, decreased after 24 hours and was increased again at three weeks. Within 30 minutes of the antibody injection an increased infiltration of monocytes-macrophages was observed in the glomeruli, which was maintained up to three weeks of induction of the glomerulonephritis. When the rats were decomple-mented with cobra venom factor prior to the i.v. injection of ATS, the expression of MCP-1 in glomeruli remained low and the influx of monocytes/macrophages did not appear. We conclude that MCP-1 is increased early on in glomeruli of rats with immune-mediated mesangial proliferative glomerulonephritis. This increase is mediated by complement activation secondary to thein situimmune complex formation at the glomerular mesangium. Elevated MCP-1 might play an important role in the recruitment of monocytes/macrophages into glomeruli followingin situimmune complex formation.