The alternative pathway of complement is activated in the glomeruli and tubulointerstitium of mice with adriamycin nephropathy

Am J Physiol Renal Physiol. 2007 Aug;293(2):F555-64. doi: 10.1152/ajprenal.00403.2006. Epub 2007 May 23.


The complement system effectively identifies and clears invasive pathogens as well as injured host cells. Uncontrolled complement activation can also contribute to tissue injury, however, and inhibition of this system may ameliorate many types of inflammatory injury. Several studies have demonstrated that the filtration of complement proteins into the renal tubules, as occurs during proteinuric renal disease, causes tubular inflammation and injury. In the present study, we tested the hypothesis that activation of the complement system in the urinary space requires an intact alternative pathway. Using a model of adriamycin-induced renal injury, which induces injury resembling focal segmental glomerulosclerosis, we examined whether mice deficient in factor B would be protected from the development of progressive tubulointerstitial injury. Complement activation was attenuated in the glomeruli and tubulointerstitium of mice with congenital deficiency of factor B (fB-/-) compared with wild-type controls, demonstrating that complement activation does occur through the alternative pathway. Deficiency in factor B did not significantly protect the mice from tubulointerstitial injury. However, treatment of wild-type mice with an inhibitory monoclonal antibody to factor B did delay the development of renal failure. These results demonstrate that complement activation in this nonimmune complex-mediated model of progressive renal disease requires an intact alternative pathway.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Albuminuria / chemically induced
  • Albuminuria / metabolism
  • Animals
  • Antibiotics, Antineoplastic / toxicity*
  • Antibodies, Monoclonal / pharmacology
  • Blotting, Western
  • Complement Factor B / antagonists & inhibitors
  • Complement Factor B / genetics
  • Complement Factor B / physiology*
  • Complement Pathway, Alternative / physiology*
  • Doxorubicin / toxicity*
  • Fluorescent Antibody Technique
  • Kidney Diseases / chemically induced*
  • Kidney Diseases / physiopathology*
  • Kidney Failure, Chronic / chemically induced
  • Kidney Failure, Chronic / pathology
  • Kidney Failure, Chronic / physiopathology
  • Kidney Function Tests
  • Kidney Glomerulus / pathology
  • Kidney Glomerulus / physiopathology*
  • Kidney Tubules / pathology
  • Kidney Tubules / physiopathology*
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Proteinuria / chemically induced
  • Proteinuria / physiopathology


  • Antibiotics, Antineoplastic
  • Antibodies, Monoclonal
  • Doxorubicin
  • Complement Factor B