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

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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