title: C5b-9 does not mediate tubulointerstitial injury in experimental acute glomerular disease characterized by selective proteinuria.
abstract: OBJECTIVE
  To determine whether complement membrane attack complex (C5b-9) has a pathogenic role in tubulointerstitial injury in a renal disease model characterized by acute highly selective proteinuria.
  
  
  METHODS
  Protein-overload nephropathy (PON) was induced in adult female Piebald-Viral-Glaxo rats with or without complement C6 deficiency (C6(-) and C6(+)) by daily intraperitoneal injections of bovine serum albumin (BSA, 2 g/d), and examined on days 2, 4 and 8.
  
  
  RESULTS
  Groups with PON developed equivalent levels of heavy proteinuria within 24 h of BSA injection. In C6(+) rats with PON, the tubulointerstitial expression of C5b-9 was increased and localized predominantly to the basolateral surface of tubular epithelial cells (TECs), whereas it was undetectable in C6(-) animals. TEC proliferation (as assessed by the number of BrdU+ cells) increased by more than 50-fold in PON, peaking on day 2 and declining on days 4 to 8. There was a trend for a reduction in the number of BrdU+ TECs on day 4 in the C6(-) PON group (P = 0.10 compared to C6(+)) but not at any other time-point. Kidney enlargement, TEC apoptosis (TUNEL(+) cells) and markers of tubular injury (tubule dilatation, loss of TEC height, protein cast formation) were not altered by C6 deficiency in PON. Interstitial monocyte (ED-1+ cell) accumulation was partially reduced in C6(-) animals with PON on day 4 (P = 0.01) but there was no change in myofibroblast accumulation.
  
  
  CONCLUSIONS
  These data suggest that C5b-9 does not mediate tubulointerstitial injury in acute glomerular diseases characterized by selective proteinuria.
authors.affiliation: Gopala K Rangan, Westmead Institute for Medical Research Level 5, Centre for Transplant and Renal Research, Sydney, NSW 2145, Australia.
authors.forename: Gopala K
authors.initials: GK
authors.lastname: Rangan
keywords: Apoptosis; C5b-9; Complement; Proliferation; Proteinuria; Rats; Tubulointerstitial