Research on The Role of Complement Regulatory Membrane Factors in The Initiation and Progression of Glomerular Injury

本研究旨在探讨补体调节膜因子（CRMFs）在肾小球损伤发病中的作用。CRMF在两个层面上工作，i。例如，C3扩增水平和膜攻击复合物（MAC）形成水平。从这个研究项目中获得了以下新发现。(1)在人和大鼠中，CRMF在正常肾脏（包括肾小球）和其他器官中均显著表达。(2)通过中和性单克隆抗体在体内系统抑制这些因子的功能导致大鼠内毒素休克样症状。这一发现首次证明了CRMF在保护宿主器官免受自发发生的补体攻击方面起着至关重要的作用。(3)使用我们实验室开发的离体肾脏灌注系统，在大鼠中实现了对肾脏中CRMF的选择性抑制。当补体依赖性肾小球损伤诱导在 关于我们 在CRMF抑制的大鼠中，肾小球损伤随着补体激活产物沉积的增加而显著增强。本研究首次在体内证实了肾小球CRMFs在肾小管间质损伤的发病机制中起保护作用，并对CRMFs在肾小管间质损伤的发病机制中的作用进行了初步研究。(1)肾小管间质CRMF的功能抑制导致肾小管间质病变的发展，没有任何补体激活刺激。因此，CRMF对于维持肾脏的正常完整性是重要的。(2)肾小管周围毛细血管中CRMF的功能抑制导致血浆蛋白的渗透性增加和肾小管间质损伤。结论：促进这一领域的研究，将大大有助于了解进行性肾损伤的机制。少

This project was performed to elusidate the in vivo role of complement regulatory membrane factors (CRMFs) in the pathegenesis of glomerular injury. CRMFs work at two levels, i. e., the level of C3 amplification and the level of formation of membrane attack complex (MAC). The following new findings were obtained from this research project. (1) Both in human and rats, CRMFs were significantly expressed in the normal kidney including glomeruli, and in other organs. (2) Systemic suppression of the function of these factors in vivo by neutralizing monoclonal antibodies result in the endotoxin shock-like symptoms in rats. It was demonstrated for the first time by this finding that CRMFs play crucial roles for the protection of host organs from the spontaneously occurring complement attack. (3) Using an isolated kidney perfusion system developed in our laboratory, selective suppression of CRMFs in the kidney was achieved in rats. When complement-dependent glomerular injury was induced in the … More se CRMF-suppressed rats, glomerular injury was significantly enhanced with increased deposition of complement activation products. From these findings, it was testified in vivo for the first time that CRMFs in the glomeruli play protective roles in the pathogenesis of this kind of glomerular injury.The following preliminary findings concerning the role of CRMFs in the pathogenesis of tubulointerstitial injury were also obtained by the present research project. (1) Functional suppression of tubulointerstitial CRMF resulted in the development of tubulointerstitial lesion without any complement-activating stimuli. Thus, CRMFs are important for maintaining the normal integrity of the kidney. (2) Functional suppression of CRMFs in the peritubular capillaries resulted in the increased permeability for plasma proteins, and in the tubulointerstitial injury. It is concluded that promotion of the research in this field must greatly contribute to the understanding of the mechanisms of progressive renal injury. Less