Liver sinusoidal endothelial cells show reduced scavenger function and downregulation of Fc gamma receptor IIb, yet maintain a preserved fenestration in the Glmpgt/gt mouse model of slowly progressing liver fibrosis
Fig 5
FcγRIIb expression in liver from Glmpgt/gt and WT mice.
A-B) FcγRII expression in liver sinusoids of A) 4 months old, and B) 9–10 months old Glmpgt/gt and WT male mice. In WT livers, positive immunostaining (red fluorescence) was seen along the sinusoids in the same cells that had taken up FITC-FSA (green fluorescence), while the expression was low or absent in Glmpgt/gt livers, including cells that had taken up FITC-FSA (arrows). Nuclei in A) are stained with DAPI (blue). Scale bars: 20 μm. C) Quantitative image analysis of FcγRII staining (% positive area) in liver sections from WT and Glmpgt/gt mice. Groups: Young WT, 3–6 months (n = 5); young Glmpgt/gt, 4 months (n = 5); old WT, 9–10 months (n = 4), and old Glmpgt/gt, 9–10 months (n = 6). Each dot represents one animal. Medians are presented as horizontal lines, and upper and lower lines represent interquartile range. *p-value < 0.05, **p-value < 0.01, One-way non-parametric ANOVA on ranks (Kruskal-Wallis test). D) Fcgr2b expression (qPCR) in liver tissue from 4 months (“young”) and 9 months (“old”) WT and Glmpgt/gt male mice (young: n = 4 per group; old: n = 3 per group). *p-value < 0.05 (Mann Whitney U test). Error bars represent standard deviation. E, F) Western blots showing FcγRII expression in whole liver lysates from E) 4 WT mice and 3 Glmpgt/gt mice, aged 4 months, and F) 4 WT mice and 3 Glmpgt/gt mice, aged 9 months, all male. LSEC: Mouse liver sinusoidal endothelial cell lysates (C57Bl/6JRj, WT). Protein loaded per lane: Liver lysates, 25 μg; LSEC, 5 μg. Beta-actin loading control was performed on the stripped blots.