Related Experiment Video
Updated: Jul 17, 2026
Rapid Depletion of Renal Macrophages Using Human CD59/Intermedilysin Cell Ablation Tool
Published on: May 9, 2025
Decay-accelerating factor but not CD59 limits experimental immune-complex glomerulonephritis
Lihua Bao1, Mark Haas, Andrew W Minto
1Section of Nephrology, The University of Chicago, Chicago, IL 60637, USA. lbao@medicine.bsd.uchicago.edu
Insights
Deficiency in decay accelerating factor (DAF) exacerbates immune complex-mediated glomerulonephritis (ICGN) by increasing C3 deposition. CD59 deficiency did not impact disease, suggesting C3 activation is key in this ICGN model.
Area of Science:
- Immunology
- Nephrology
- Complement System Biology
Background:
- The complement system plays a dual role in immune complex-mediated glomerulonephritis (ICGN), with both activating and regulatory proteins influencing disease pathogenesis.
- Decay accelerating factor (DAF) and CD59 are key regulators, inhibiting C3 activation and C5b-9 generation, respectively.
- These proteins are widely distributed cell membrane proteins crucial for immune regulation.
Purpose of the Study:
- To investigate the role of DAF and CD59 in the development of experimental ICGN.
- To determine the relative importance of C3 activation versus C5b-9 generation in ICGN pathogenesis.
- To assess the impact of DAF and CD59 deficiency on glomerular inflammation and injury.
Main Methods:
- Induction of chronic serum sickness and ICGN in DAF-deficient, CD59-deficient, and DAF/CD59-deficient mice.
- Comparison of disease incidence and severity with wild-type littermate controls.
- Analysis of glomerular C3 deposition, monocyte chemoattractant protein-1 mRNA expression, and leukocyte infiltration.
Main Results:
- DAF-deficient and DAF/CD59-deficient mice exhibited a higher incidence of glomerulonephritis (GN) with increased glomerular C3 deposition compared to controls.
- CD59-deficient mice showed no significant difference in disease expression compared to wild-type mice.
- DAF-deficient mice displayed elevated monocyte chemoattractant protein-1 mRNA and increased glomerular leukocyte infiltration.
Conclusions:
- C3 activation is strongly implicated in the pathogenesis of experimental ICGN.
- The terminal complement pathway component C5b-9 appears to have a lesser pathogenic role in this specific ICGN model.
- DAF deficiency significantly contributes to the development of ICGN, highlighting its regulatory importance.
Abstract:
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/CD59-deficient 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.
