title: Reduction of renal fibrosis as a result of liposome encapsulated clodronate induced macrophage depletion after unilateral ureteral obstruction in rats.
abstract: OBJECTIVE
  Macrophages have been thought to play a role in renal tubulointerstitial fibrosis; recent reports have demonstrated an antifibrotic effect of macrophages in late-stage renal fibrosis. Liposome-encapsulated clodronate (LC) produces a selective and systemic depletion of phagocytic macrophages in vivo. To study the role of initial infiltrating macrophages in renal fibrosis, we compared the effects of pretreatment with LC and a liposome vehicle for control of the severity of renal fibrosis in a unilateral ureteral obstruction (UUO) rat model.
  
  
  METHODS
  One day after a single intravenous injection of LC or liposome vehicle, the rats underwent UUO. Following 1, 5, and 14 days, the kidneys were examined to evaluate macrophage infiltration and renal fibrosis.
  
  
  RESULTS
  LC depleted macrophages systemically and reduced renal fibrosis associated with UUO; this beneficial effect was accompanied by a decrease of transforming growth factor beta mRNA expression. The osteopontin expression was also reduced by pretreatment with LC.
  
  
  CONCLUSIONS
  Initial interstitial infiltration of macrophages contributes to tubulointerstitial fibrosis in UUO.
authors.affiliation: Division of Nephrology, Eulji Hospital, Seoul, Korea.
authors.forename: Su Ah
authors.initials: SA
authors.lastname: Sung
authors.forename: Sang Kyung
authors.initials: SK
authors.lastname: Jo
authors.forename: Won Yong
authors.initials: WY
authors.lastname: Cho
authors.forename: Nam Hee
authors.initials: NH
authors.lastname: Won
authors.forename: Hyoung Kyu
authors.initials: HK
authors.lastname: Kim
mesh_terms: D000818:Animals; D004002:Clodronic Acid / Q000008:administration & dosage*; D005355:Fibrosis; D007668:Kidney / Q000473:pathology*; D008081:Liposomes; D008264:Macrophages / Q000187:drug effects / Q000502:physiology*; D008297:Male; D053495:Osteopontin / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D016212:Transforming Growth Factor beta / Q000032:analysis; D014517:Ureteral Obstruction / Q000150:complications*
chemical_list: D008081:Liposomes; D016212:Transforming Growth Factor beta; D004002:Clodronic Acid; D053495:Osteopontin