Decay-accelerating factor but not CD59 limits experimental immune-complex glomerulonephritis
Decay-accelerating factor but not CD59 limits experimental immune-complex glomerulonephritis
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DOI：
10.1038/labinvest.3700522
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发表时间：
2007-04-01
影响因子：
5
通讯作者：
Quigg, Richard J.
中科院分区：
文献类型：
--
作者：
Bao, Lihua;Haas, Mark;Quigg, Richard J.
补体系统的促活化和调节影响之间的复杂平衡可以影响免疫复合物介导的肾小球肾炎（ICGN）的发病机制。关键的补体调节蛋白包括衰变加速因子（decay accelerating factor，CD 59），它们分别抑制C3活化和C5 b-9生成。两者都是糖基磷脂酰肌醇连接的细胞膜蛋白，广泛分布于人类和小鼠中。用马脾脱铁铁蛋白每日免疫6周诱导的慢性血清病用于诱导CD 59、CD 59和CD 59/CD 59缺陷小鼠的ICGN，野生型同窝小鼠作为对照。与野生型对照组相比，β 2受体和β 2受体/CD 59缺陷小鼠的GN发病率均增加，并伴有肾小球C3沉积显著增加。CD 59缺陷小鼠的疾病表达与野生型对照没有区别。CD 45和CD 45/CD 59缺陷小鼠也有单核细胞趋化蛋白-1 mRNA表达增加和肾小球浸润CD 45（+）白细胞。我们的研究结果表明，C3的激活与实验性ICGN密切相关，而下游形成的C5 b-9在该模型中的致病重要性较小。
The complex balance between the pro-activating and regulatory influences of the complement system can affect the pathogenesis of immune complex-mediated glomerulonephritis (ICGN). Key complement regulatory proteins include decay accelerating factor (DAF) and CD59, which inhibit C3 activation and C5b-9 generation, respectively. Both are glycosylphosphatidylinositol-linked cell membrane proteins, which are widely distributed in humans and mice. Chronic serum sickness induced by daily immunization with horse spleen apoferritin over 6 weeks was used to induce ICGN in DAF-, CD59- and DAF/CD59-deficient mice, with wild-type littermate mice serving as controls. Both DAF and DAF/CD59deficient mice had an increased incidence of GN relative to wild-type controls associated with significantly increased glomerular C3 deposition. Disease expression in CD59-deficient mice was no different than wild- type controls. DAF- and DAF/CD59-deficient mice also had increased monocyte chemoattractant protein-1 mRNA expression and glomerular infiltration with CD45(+) leukocytes. Our findings suggest that activation of C3 is strongly associated with experimental ICGN while downstream formation of C5b-9 is of lesser pathogenic importance in this model.