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.

• Authors: Jin H Kim, Dong-Won Lee, Myeong H Jung, Hyun-Seop Cho, Dae-Hong Jeon, Se-Ho Chang, Dong Jun Park
• Journal: Nephron. Experimental nephrology (Nephron Exp Nephrol) Vol. 128 Issue 1-2 Pg. 21-9 ( 2014) ISSN: 1660-2129 [Electronic] Switzerland
• PMID: 25376384 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2014 S. Karger AG, Basel.

Chemical References

• Cytokines
• Liposomes
• Clodronic Acid
• Nitric Oxide
• Glycerol

Topics

• Acute Kidney Injury (chemically induced, pathology, prevention & control)
• Administration, Intravenous
• Animals
• Apoptosis (drug effects)
• Clodronic Acid (administration & dosage, pharmacology)
• Cytokines (metabolism)
• Disease Models, Animal
• Epithelial Cells (drug effects, pathology)
• Glycerol (administration & dosage, adverse effects, pharmacology)
• Injections, Intramuscular
• Kidney Tubules (drug effects, pathology)
• Liposomes (administration & dosage, pharmacology)
• Macrophages (drug effects, pathology)
• Male
• Mice
• Mice, Inbred C57BL
• Nitric Oxide (metabolism)
• Rhabdomyolysis (chemically induced, pathology, prevention & control)