ConA-induced hepatic injury in HSC-depleted mice. HSC-sufficient and HSC-depleted mice were administered 20 mg/kg ConA, and euthanized 6 hours later. A–C: Representative hematoxylin and eosin (H&E)— (A) or TUNEL— (B) stained sections, and serum alanine aminotransferase (ALT) levels (C) are shown. Areas marked by dashed lines (left panel) and solid yellow arrowheads (right panel) in A depict necrotic damage and cell death, respectively. In HSC-depleted mice (middle panel), no defined necrotic areas could be seen. Solid white arrowheads (bottom panel) in B depict TUNEL+ nuclei. Numerous TUNEL+ cells can be seen in ConA-treated HSC-sufficient mice (top panel). D: H&E-stained liver sections show robust sinusoidal congestion and inflammation in both portal and central areas of HSC-sufficient mice, which are strongly reduced in the HSC-depleted mice. E: Sinusoidal congestion and midzonal necrosis induced by ConA in HSC-sufficient mice is minimal in HSC-depleted mice. Area marked by dashed line depicts necrotic damage. Data are expressed as means ± SD (B and C). n = 6 to 8 per group. *P < 0.05, ***P < 0.001 versus control; ††P < 0.01 versus HSC-depleted mice. Scale bars: 100 μm (A, left and middle panels); 20 μm (A, right panel, D, and E); 50 μm (B). CV, central vein; PV, portal vein.