title: The role of macrophage in the pathogenesis of chronic cyclosporine-induced nephropathy.
abstract: BACKGROUND
  Macrophages play diverse roles in tissue injury. We evaluated their role in cyclosporine (CsA)-induced renal injury by depletion with liposomal clodronate (CL).
  
  
  METHODS
  Male Sprague Dawley rats were treated with CsA with or without CL treatment for 28 days. We assessed responses from the pathology and by measuring renal functions and levels of a proinflammatory cytokine (osteopontin), a profibrotic cytokine (betaig-h3), innate immune response markers (toll-like receptor 2 and MHC class II molecules), apoptotic cell death (deoxynucleotidyl transferase-mediated dUTP-biotin nick end-labelling staining and caspase-3 expression) and oxidative stress (8-hydroxy-2'-deoxyguanosine, 8-OHdG).
  
  
  RESULTS
  Macrophage depletion with CL improved not only renal function but also histopathology compared with the CsA-treated rats. Osteopontin and betaig-h3 levels increased significantly in CsA-treated rat kidneys, but CL treatment decreased both markers. Enhanced innate immune response and apoptotic cell death in CsA-treated rat kidney were decreased with CL. The increased rates of urinary 8-OHdG excretion and the tubular expression of 8-OHdG produced by CsA treatment were reversed with CL treatment.
  
  
  CONCLUSIONS
  Thus, infiltrating macrophages were involved in both nonimmunologic and immunologic injury and led to apoptotic cell death in this rat model of chronic CsA nephropathy.
authors.affiliation: Department of Internal Medicine, Catholic University of Korea, Seoul 137-040, Korea.
authors.forename: Jung Yeon
authors.initials: JY
authors.lastname: Ghee
authors.forename: Dong He
authors.initials: DH
authors.lastname: Han
authors.forename: Hyun Kuk
authors.initials: HK
authors.lastname: Song
authors.forename: Wan Young
authors.initials: WY
authors.lastname: Kim
authors.forename: Su Hyun
authors.initials: SH
authors.lastname: Kim
authors.forename: Hye Eun
authors.initials: HE
authors.lastname: Yoon
authors.forename: Bum Soon
authors.initials: BS
authors.lastname: Choi
authors.forename: Yong Soo
authors.initials: YS
authors.lastname: Kim
authors.forename: Jin
authors.initials: J
authors.lastname: Kim
authors.forename: Chul Woo
authors.initials: CW
authors.lastname: Yang
mesh_terms: D000818:Animals; D017209:Apoptosis; D002908:Chronic Disease; D004002:Clodronic Acid / Q000008:administration & dosage; D016572:Cyclosporine / Q000633:toxicity*; D007113:Immunity, Innate; D007166:Immunosuppressive Agents / Q000633:toxicity; D007668:Kidney / Q000187:drug effects / Q000276:immunology / Q000293:injuries / Q000473:pathology; D007674:Kidney Diseases / Q000139:chemically induced* / Q000276:immunology / Q000473:pathology / Q000503:physiopathology*; D008081:Liposomes; D008264:Macrophages / Q000187:drug effects / Q000276:immunology / Q000502:physiology*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D007166:Immunosuppressive Agents; D008081:Liposomes; D004002:Clodronic Acid; D016572:Cyclosporine