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Updated: Apr 21, 2026
Rapid Depletion of Renal Macrophages Using Human CD59/Intermedilysin Cell Ablation Tool
Published on: May 9, 2025
Macrophage depletion ameliorates glycerol-induced acute kidney injury in mice
Jin H Kim1, Dong-Won Lee, Myeong H Jung
1Biomedical Research Institute, Gyeongsang National University, Jinju, Republic of Korea.
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.
Insights
Depleting renal macrophages using liposome-encapsulated clodronate (LEC) significantly protects against acute kidney injury (AKI) in a mouse model. Macrophage depletion reduces tubular apoptosis and inflammation, preventing kidney dysfunction.
Area of Science:
- Nephrology
- Immunology
- Cell Biology
Background:
- Acute kidney injury (AKI) pathogenesis involves complex cellular and inflammatory processes.
- Renal macrophages play a critical, yet not fully understood, role in AKI development.
- Investigating macrophage function is crucial for developing targeted AKI therapies.
Purpose of the Study:
- To elucidate the specific role of renal macrophages in glycerol-induced rhabdomyolysis and subsequent AKI.
- To evaluate the therapeutic potential of macrophage depletion in preventing AKI.
- To analyze the molecular mechanisms underlying macrophage-mediated kidney injury.
Main Methods:
- Established a mouse model of AKI using intramuscular glycerol injection.
- Utilized liposome-encapsulated clodronate (LEC) for targeted renal macrophage depletion.
- Assessed kidney injury markers, tubular cell apoptosis, and inflammatory mediator expression post-treatment.
Main Results:
- Glycerol injection induced significant renal dysfunction and tubular damage, evidenced by increased serum creatinine.
- Macrophage depletion with LEC markedly reduced the number of renal macrophages (CD45(+)CD11b(+)Ly6c(+) and F4/80(+)).
- LEC pretreatment attenuated glycerol-induced tubular cell apoptosis (decreased caspase-9, p53; increased Bcl-2) and suppressed key inflammatory pathways (NF-κB, MCP-1, ICAM-1, iNOS, COX-2).
Conclusions:
- Renal macrophages are key contributors to AKI development in this rhabdomyolysis model.
- Depletion of renal macrophages effectively prevents AKI by inhibiting tubular cell apoptosis.
- Targeting renal macrophages represents a promising therapeutic strategy for mitigating AKI and renal dysfunction.
