Macrophage depletion ameliorates glycerol-induced acute kidney injury in mice.
BACKGROUND
This study was conducted to elucidate the role of renal macrophages in the development of acute kidney injury (AKI) in a glycerol (Gly)-induced rhabdomyolysis mouse model.


METHODS
The experimental model of rhabdomyolysis requires injecting 50% Gly (10 ml/kg) intramuscularly into mice. Control mice were injected into the tail vein with the liposomal vehicle. Liposome-encapsulated clodronate (LEC)-only mice were injected with LEC. Gly-only mice were injected with Gly into a hind limb. LEC+Gly-treated mice were injected intravenously with 100 μl of LEC 24 h prior to Gly injection. Mice were sacrificed 24 h after Gly injection.


RESULTS
Gly injection increased the serum creatinine level, and induced tubular damage. Renal CD45(+)CD11b(+)Ly6c(+) or CD45(+)CD11b(+)Ly6c(+)F4/80(+) macrophages were decreased by pretreatment with LEC in both normal and injured kidneys. Macrophage depletion prevented Gly-induced apoptotic death of tubular epithelial cells by decreasing caspase-9, ERK and p53, while increasing Bcl-2 expression. Expression of the inflammatory mediators NF-κB, MCP-1, ICAM-1, iNOS and COX-2 were also decreased with LEC pretreatment of mice injected with Gly.


CONCLUSIONS
These results support the hypothesis that depletion of macrophages prevents renal dysfunction by abrogating apoptosis and attenuating inflammation during AKI.
Biomedical Research Institute, Gyeongsang National University, Jinju, Republic of Korea.
Jin H
JH
Kim
Dong-Won
DW
Lee
Myeong H
MH
Jung
Hyun-Seop
HS
Cho
Dae-Hong
DH
Jeon
Se-Ho
SH
Chang
Dong Jun
DJ
Park
D058186:Acute Kidney Injury / Q000139:chemically induced* / Q000473:pathology / Q000517:prevention & control*; D061605:Administration, Intravenous; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D004002:Clodronic Acid / Q000008:administration & dosage / Q000494:pharmacology*; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D004847:Epithelial Cells / Q000187:drug effects / Q000473:pathology; D005990:Glycerol / Q000008:administration & dosage / Q000009:adverse effects* / Q000494:pharmacology; D007273:Injections, Intramuscular; D007684:Kidney Tubules / Q000187:drug effects / Q000473:pathology; D008081:Liposomes / Q000008:administration & dosage / Q000494:pharmacology*; D008264:Macrophages / Q000187:drug effects / Q000473:pathology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009569:Nitric Oxide / Q000378:metabolism; D012206:Rhabdomyolysis / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control
D016207:Cytokines; D008081:Liposomes; D004002:Clodronic Acid; D009569:Nitric Oxide; D005990:Glycerol