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.
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 rhabdomyolysismouse 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: Ravindra Boddu; Travis D Hull; Subhashini Bolisetty; Xianzhen Hu; Mark S Moehle; João Paulo Lima Daher; Ahmed Ibrahim Kamal; Reny Joseph; James F George; Anupam Agarwal; Lisa M Curtis; Andrew B West Journal: Hum Mol Genet Date: 2015-04-22 Impact factor: 6.150
Authors: Alfonso Rubio-Navarro; Melania Guerrero-Hue; Beatriz Martín-Fernandez; Isabel Cortegano; Elena Olivares-Alvaro; Natalia de Las Heras; Mario Alía; Belén de Andrés; María Luisa Gaspar; Jesús Egido; Juan Antonio Moreno Journal: J Vis Exp Date: 2016-10-18 Impact factor: 1.355
Authors: Alfonso Rubio-Navarro; Mónica Carril; Daniel Padro; Melanie Guerrero-Hue; Carlos Tarín; Rafael Samaniego; Pablo Cannata; Ainhoa Cano; Juan Manuel Amaro Villalobos; Ángel Manuel Sevillano; Claudia Yuste; Eduardo Gutiérrez; Manuel Praga; Jesús Egido; Juan Antonio Moreno Journal: Theranostics Date: 2016-04-21 Impact factor: 11.556