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. 2023 Mar 31;16(1):17–37. doi: 10.1016/j.jcmgh.2023.03.007

Figure 8.

Figure 8

Efficacy and safety of Axl inhibition in a carbon tetrachloride-induced liver fibrosis model. (A) Overview of carbon tetrachloride (CCl4) model involving biweekly administration of CCl4 (intraperitoneal 0.4 mL/kg) for 6 weeks and therapeutic immunomodulation with bemcentinib for 1 week every other day (intraperitoneal 100 mg/kg). (B) Flow cytometry gating strategies for liver cell subsets including infiltrating monocytes, monocyte-derived macrophages (MoMF), and Kupffer cells (KCs) in a wild-type (wt) and CCl4 mouse model. (C) Monocyte/macrophage cell numbers per gram of liver tissue in healthy controls and CCl4 model. (D) Flow cytometry analysis of Axl expression levels displayed as either % or median fluorescence intensity (MFI) on liver cell subsets identified in B. (E) Representative micrographs from either Axl/F4/80/DAPI stains or Mertk/F4/80/DAPI stains of mouse livers from healthy controls and CCl4-treated animals. (F) Percentage of either Axl-expressing macrophages or Mertk-expressing macrophages relative to total population (mean per mouse). (G) Flow cytometry gating strategy for blood monocytes. (H) Flow cytometry analysis of either Axl or Mertk expression levels displayed as % or MFI on blood monocytes identified in G. (I) Representative images of hematoxylin-eosin stainings (above) and Sirius Red stainings (below) of FFPE liver sections from either healthy controls or CCl4-treated mice with or without bemcentinib treatment. (J) Liver necroinflammation score (Ishak grade) and liver fibrosis score (Ishak stage) based on histopathology analysis of H&E and Sirius Red stainings. (K) Plasma levels of bilirubin, albumin, and alanine aminotransferase (ALT) assessed with a clinical chemistry analyzer. (L) Cells per gram of liver tissue from CCl4-treated mice after administration of bemcentinib. (M) Axl and Mertk (% and MFI values) on either liver monocytes/macrophages or blood monocytes assessed with flow cytometry analysis. ns = not significant/∗P < .05/∗∗P < .01, unpaired t tests and one-way ordinary analysis of variance. AF594, red; AF488, green; DAPI, blue; scale bar = 50 μm.