Macrophage Depletion Ameliorates Glycerol-Induced Acute Kidney Injury in Mice

Abstract

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.