Decay-accelerating factor but not CD59 limits experimental immune-complex glomerulonephritis.
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.
Bao
Lihua
L
Section of Nephrology, The University of Chicago, Chicago, IL 60637, USA. lbao@medicine.bsd.uchicago.edu
Haas
Mark
M
Minto
Andrew W
AW
Quigg
Richard J
RJ
D000818:Animals; D001052:Apoferritins; D001806:Blood Urea Nitrogen; D018958:CD55 Antigens / Q000235:genetics / Q000502:physiology*; D018957:CD59 Antigens / Q000235:genetics / Q000502:physiology*; D018932:Chemokine CCL2 / Q000378:metabolism; D002908:Chronic Disease; D003167:Complement Activation / Q000276:immunology*; D003176:Complement C3 / Q000276:immunology; D015936:Complement C5a / Q000276:immunology; D015938:Complement Membrane Attack Complex / Q000276:immunology; D004195:Disease Models, Animal; D005921:Glomerulonephritis / Q000139:chemically induced / Q000276:immunology / Q000473:pathology*; D006736:Horses; D007678:Kidney Glomerulus / Q000276:immunology / Q000473:pathology; D017493:Leukocyte Common Antigens / Q000276:immunology; D007962:Leukocytes / Q000276:immunology; D051379:Mice; D018345:Mice, Knockout; D012713:Serum Sickness / Q000139:chemically induced / Q000276:immunology / Q000473:pathology*
D018958:CD55 Antigens; D018957:CD59 Antigens; C491768:Ccl2 protein, mouse; D018932:Chemokine CCL2; D003176:Complement C3; D015938:Complement Membrane Attack Complex; D015936:Complement C5a; D001052:Apoferritins; D017493:Leukocyte Common Antigens; C516770:Ptprc protein, mouse