Activation of intrarenal complement system in mouse model for chronic cyclosporine nephrotoxicity.
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.
Kim
Young Ok
YO
Department of Internal Medicine, The Catholic University of Korea, Seoul, Korea.
Lim
Sun Woo
SW
Li
Can
C
Kang
Hee Jung
HJ
Ahn
Kyung Ohk
KO
Yang
Hyun Joo
HJ
Ghee
Jung Yeon
JY
Kim
Su Hyun
SH
Kim
Jin Young
JY
Choi
Bum Soon
BS
Kim
Jin
J
Yang
Chul Woo
CW
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
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