Ichida S, Yuzawa Y, Okada H, Yoshioka K, Matsuo S
Third Department of Internal Medicine, Nagoya University School of Medicine, Japan.
Kidney Int. 1994 Jul;46(1):89-96. doi: 10.1038/ki.1994.247.
The kidney is an organ where complement-mediated tissue injuries take place by various stimuli. To assess how the kidney is protected from the autologous complement attack, comparative localization of decay accelerating factor (DAF), membrane cofactor protein (MCP) and 20 kDa homologous restriction factor (HRF20) was studied in the normal human kidney. Specific monoclonal antibodies to DAF, MCP and HRF20 were used for the study. Studies by immunofluorescence and immunoelectron microscopy showed that the distribution of each protein in the kidney was complementary to each other in most parts. MCP and HRF20 were clearly seen in the glomerular capillaries, while DAF was only faintly observed. Juxtaglomerular apparatus was abundant in DAF and MCP but not in HRF20. HRF20 was most strongly expressed in the peritubular capillaries where MCP was not detectable. Basolateral membranes of the proximal tubules and collecting ducts expressed MCP strongly, while there was no expression of DAF in the proximal tubules. Interestingly, both DAF and MCP, which inhibit complement activation at C3/C4 level, were not expressed in the apical portion of the tubular cells including proximal tubule brush border. In contrast, HRF20 was expressed on the apical part of the tubules. Medullary interstitium strongly expressed MCP but not DAF. Based on these observations, we conclude that each segment of the kidney is protected from the complement attack by the different combination of complement regulatory proteins. We speculate that the tubular cells might be fragile when complements are activated inside the tubular lumen, because there is no expression of complement regulatory proteins which inhibit C3 convertase.
肾脏是一个因各种刺激而发生补体介导的组织损伤的器官。为了评估肾脏如何免受自身补体攻击，我们研究了衰变加速因子（DAF）、膜辅因子蛋白（MCP）和20 kDa同源限制因子（HRF20）在正常人类肾脏中的比较定位。使用了针对DAF、MCP和HRF20的特异性单克隆抗体进行研究。免疫荧光和免疫电子显微镜研究表明，每种蛋白质在肾脏中的分布在大多数部位相互补充。MCP和HRF20在肾小球毛细血管中清晰可见，而DAF仅微弱观察到。近球小体中DAF和MCP丰富，但HRF20不存在。HRF20在肾小管周围毛细血管中表达最强，而在那里检测不到MCP。近端小管和集合管的基底外侧膜强烈表达MCP，而近端小管中没有DAF的表达。有趣的是，在包括近端小管刷状缘在内的肾小管细胞顶端部分，抑制C3/C4水平补体激活的DAF和MCP均未表达。相反，HRF20在肾小管顶端部分表达。髓质间质强烈表达MCP但不表达DAF。基于这些观察结果，我们得出结论，肾脏的每个节段通过补体调节蛋白的不同组合免受补体攻击。我们推测当补体在肾小管腔内被激活时，肾小管细胞可能很脆弱，因为没有抑制C3转化酶的补体调节蛋白的表达。
