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. 2017 Mar 22;114(14):E2862–E2871. doi: 10.1073/pnas.1618291114

Fig. 3.

Fig. 3.

Relevance of FcRn deficiency in an APAP toxicity model. (A) Bile and serum levels of mouse albumin in Fcgrt−/−, Fcgrt+/+, and FCGRTTG mice (n = 4–7 mice per group; ***P < 0.001). (B) Survival curves after lethal APAP administration (600 mg/kg) in Fcgrt−/− (n = 14), Fcgrt+/+ (n = 12), and FCGRTTG (n = 13) (*P = 0.0486). (C) Excretion of APAP into the bile after a lethal dose of APAP in Fcgrt+/+, Fcgrt−/−, and FCGRTTG mice (n = 4 per group; *P < 0.05, **P < 0.01). (D) Serum APAP levels in WT and Fcgrt−/− mice after a lethal dose of APAP (n = 7 per group; *P = 0.0185 **P = 0.0049). (E) Serum ALT levels 8 h after sublethal APAP administration (400 mg/kg) to Fcgrt−/−, Fcgrt+/+, and FCGRTTG mice (n = 5–6; ***P < 0.001). (F) Survival curves after lethal APAP administration (600 mg/kg) to WT (Fcgrtfl/fl-WT) and Fcgrt liver-specific–deficient (Fcgrtfl/flAlbCre) mice (n = 5–9; *P < 0.05). (G and H) Serum ALT (G) and APAP (H) levels 8 h after sublethal APAP administration (400 mg/kg) to Fcgrtfl/fl-WT and Fcgrtfl/fl-AlbCre mice [n = 9 or 10, pooled from three experiments (G) or n = 4 (H), *P < 0.05]. (I) Intracellular levels of ROS in Fcgrt+/+ or Fcgrt−/− mouse primary hepatocytes (****P < 0.0001). Levels of oxidative stress were determined using a cell-permeable fluorescence probe, the chloromethyl derivative of H2DCF-DA (CM-H2DCF-DA), which is oxidized to fluorescent DCF. Cells were left untreated or were treated with different concentrations of H2O2 to increase intracellular levels of oxidative stress. The percent of change (%Δ) in ROS was calculated by subtracting the DCF mean fluorescence intensity (MFI) of untreated cells from the DCF MFI of H2O2-treated cells. (J) Serum ALT levels 8 h after administration of two different sublethal doses of APAP (300 and 450 mg/kg) in Alb−/−, Alb+/+Fcgrt+/+, and Fcgrt−/− mice (n = 4–5; *P = 0.019; **P < 0.0013; ***P = 0.0006; ****P < 0.00011). Open circles represent biological replicates. Data were statistically analyzed by one-way ANOVA (A and E), two-way ANOVA (I), unpaired Student t test (C, D, G, H, and J), or Mantel–Cox test (B and F). IQR, interquartile range; U/L, units per liter.