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.

CONCLUSION

These results support the hypothesis that depletion of macrophages prevents renal dysfunction by abrogating apoptosis and attenuating inflammation during AKI.