title: Activation of intrarenal complement system in mouse model for chronic cyclosporine nephrotoxicity.
abstract: OBJECTIVE
  Local activation of the complement system plays a role in target organ damage. The aim of our study was to investigate the influence of cyclosporine (CsA)- induced renal injury on the complement system in the kidney.
  
  
  METHODS
  Mice fed a low salt (0.01%) diet were treated with vehicle (VH, olive oil, 1 mL/kg/day) or CsA (30 mg/kg/day) for one or four weeks. Induction of chronic CsA nephrotoxicity was evaluated with renal function and histomorphology. Activation of the complement system was assessed through analysis of the expression of C3, C4d, and membrane attack complex (MAC), and the regulatory proteins, CD46 and CD55. CsA treatment induced renal dysfunction and typical morphology (tubulointerstitial inflammation and fibrosis) at four weeks.
  
  
  RESULTS
  CsA-induced renal injury was associated with increased the expression of C3, C4d, and MAC (C9 and upregulation of complement regulatory proteins (CD 46 and CD55). Immunohistochemistry revealed that the activated complement components were mainly confined to the injured tubulointerstitium.
  
  
  CONCLUSIONS
  CsA-induced renal injury is associated with activation of the intrarenal complement system.
authors.affiliation: Department of Internal Medicine, The Catholic University of Korea, Seoul, Korea.
authors.forename: Young Ok
authors.initials: YO
authors.lastname: Kim
authors.forename: Sun Woo
authors.initials: SW
authors.lastname: Lim
authors.forename: Can
authors.initials: C
authors.lastname: Li
authors.forename: Hee Jung
authors.initials: HJ
authors.lastname: Kang
authors.forename: Kyung Ohk
authors.initials: KO
authors.lastname: Ahn
authors.forename: Hyun Joo
authors.initials: HJ
authors.lastname: Yang
authors.forename: Jung Yeon
authors.initials: JY
authors.lastname: Ghee
authors.forename: Su Hyun
authors.initials: SH
authors.lastname: Kim
authors.forename: Jin Young
authors.initials: JY
authors.lastname: Kim
authors.forename: Bum Soon
authors.initials: BS
authors.lastname: Choi
authors.forename: Jin
authors.initials: J
authors.lastname: Kim
authors.forename: Chul Woo
authors.initials: CW
authors.lastname: Yang
mesh_terms: D000818:Animals; D018958:CD55 Antigens / Q000032:analysis; D003176:Complement C3 / Q000032:analysis; D015935:Complement C4b / Q000032:analysis; D015938:Complement Membrane Attack Complex / Q000032:analysis; D003165:Complement System Proteins / Q000032:analysis*; D016572:Cyclosporine / Q000633:toxicity*; D004195:Disease Models, Animal; D007113:Immunity, Innate / Q000187:drug effects; D015151:Immunoblotting; D007150:Immunohistochemistry; D007166:Immunosuppressive Agents / Q000633:toxicity; D007668:Kidney / Q000187:drug effects* / Q000276:immunology / Q000473:pathology; D007674:Kidney Diseases / Q000139:chemically induced* / Q000276:immunology; D017493:Leukocyte Common Antigens / Q000032:analysis; D051916:Membrane Cofactor Protein / Q000032:analysis; D051379:Mice; D018613:Microscopy, Confocal; D010446:Peptide Fragments / Q000032:analysis
chemical_list: D018958:CD55 Antigens; D003176:Complement C3; D015938:Complement Membrane Attack Complex; D007166:Immunosuppressive Agents; D051916:Membrane Cofactor Protein; D010446:Peptide Fragments; D015935:Complement C4b; C032261:complement C4d; D016572:Cyclosporine; D003165:Complement System Proteins; D017493:Leukocyte Common Antigens