Reduction of renal fibrosis as a result of liposome encapsulated clodronate induced macrophage depletion after unilateral ureteral obstruction in rats.
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.
Sung
Su Ah
SA
Division of Nephrology, Eulji Hospital, Seoul, Korea.
Jo
Sang Kyung
SK
Cho
Won Yong
WY
Won
Nam Hee
NH
Kim
Hyoung Kyu
HK
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*
D008081:Liposomes; D016212:Transforming Growth Factor beta; D004002:Clodronic Acid; D053495:Osteopontin