Fig. 2

Deletion of macrophages with clodronate liposomes (CL) aggravates APAP-induced liver injury and delays liver repair. A Representative microphotographs of immunostaining of CD68 (red) in the livers from WT and TP^−/− mice 48 h after APAP treatment. CV central vein. Scale bars: 100 μm. The number of CD68⁺ cells (macrophages) in the livers from WT and TP^−/− mice after APAP treatment. Data are expressed as the mean ± SD (n = 5–6 mice per group). **p < 0.01. B Representative dot plots of liver macrophages (F4/80⁺/CD11b⁺ cells) gated out CD45⁺/Ly6G^high/CD11b^high cells and number of macrophages 0 and 48 h after APAP treatment in WT and TP^−/− mice. Data are expressed as the mean ± SD (n = 5–6 mice per group). **p < 0.01. C The number of CD68⁺ macrophages expressing TP (TP⁺/CD68⁺ cells) in the livers from WT mice after APAP treatment. Data are expressed as the mean ± SD (n = 4–5 mice per group). ****p < 0.0001. D Expression of mRNA encoding genes related to a pro-inflammatory macrophage phenotype (Tnfa, Il1b,and Il6) in cultured BM-derived macrophages from WT and TP^−/− mice stimulated with LPS for 3 h. Data are expressed as the mean ± SD (n = 6 mice per group). ***p < 0.001; ****p < 0.0001. E Levels of ALT and hepatic necrotic area 48 h after APAP treatment in WT mice treated with clodronate liposomes (CL) or control liposomes (Cont). Data are expressed as the mean ± SD (n = 4 mice per group). **p < 0.01; ****p < 0.0001. Representative images of H&E staining of WT mice treated with CL or Cont. CV central vein, PV portal vein. Scale bars: 200 μm. F PCNA⁺ hepatocytes (%) 48 h after APAP treatment in WT mice treated with CL or Cont. Representative images showing immunohistochemical staining for PCNA in WT mice treated with CL or Cont. PV portal vein. Scale bars: 100 μm. Data are expressed as the mean ± SD (n = 4 mice per group). **p < 0.01