C5b-9 membrane attack complex mediates endothelial cell apoptosis in experimental glomerulonephritis

Am J Physiol Renal Physiol. 2000 May;278(5):F747-57. doi: 10.1152/ajprenal.2000.278.5.F747.


We studied the role of the C5b-9 membrane attack complex in two models of inflammatory glomerulonephritis (GN) initiated by acute glomerular endothelial injury in Piebold-viral-Glaxo (PVG) complement-sufficient rats (C+), C6-deficient rats (C6-), and rats systematically depleted of complement with cobra venom factor (CVF). GN was induced by performing a left nephrectomy and selectively perfusing the right kidney with either 1) the lectin concanavalin A (Con A) followed by complement-fixing anti-Con A (Con A GN) or 2) purified complement-fixing goat anti-rat glomerular endothelial cell (GEN) antibody [immune-mediated thrombotic microangiopathy (ITM)]. Comparable levels of GEN apoptosis were detected in C+ animals in both models. CVF administration reduced GEN apoptosis by 10- to 12-fold. GEN apoptosis was C5b-9 dependent because PVG C6- rats were protected from GEN loss. Furthermore, functional inhibition of the cell surface complement regulatory protein CD59 by renal perfusion with anti-CD59 antibody in ITM resulted in a 3.5-fold increase in GEN apoptosis. Last, in Con A GN, abrogation of GEN apoptosis preserved endothelial integrity and renal function. This study demonstrates the specific role of C5b-9 in the induction of GEN apoptosis in experimental inflammatory GN, a finding with implications for diseases associated with the presence of antiendothelial cell antibodies.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Apoptosis / immunology*
  • Complement C6 / deficiency
  • Complement C6 / metabolism
  • Complement Membrane Attack Complex / metabolism*
  • Concanavalin A / toxicity
  • Disease Models, Animal
  • Endothelium / immunology
  • Endothelium / pathology
  • Glomerulonephritis / immunology*
  • Glomerulonephritis / pathology*
  • Kidney Glomerulus / immunology
  • Kidney Glomerulus / pathology
  • Male
  • Rats
  • Thrombosis / immunology
  • Thrombosis / pathology


  • Complement C6
  • Complement Membrane Attack Complex
  • Concanavalin A