Figure 4. In vivo model of hepatocyte apoptosis and phagocytosis.

To follow the fate of apoptotic hepatocytes, mice were first injected with the α1-AT-LV-GFP via the portal vein then 7 days later Ad-TRAIL was injected into the tail vein of the same mice. As control, mice were injected only with Ad-TRAIL, or Ad-GFP (images not shown) or with α1-AT-LV-GFP. To inhibit apoptosis, a separate group of mice were injected with Q-VD-OPH, pancaspase inhibitor before and after the Ad-TRAIL injection. The liver from only Ad-TRAIL, or LV-injected mice showed no significant injury or infiltration by inflammatory cells, and the ALT values remained normal (Figure 4b, c). In the LV plus Ad-TRAIL-injected animals the liver showed mild to moderate hepatocyte injury, increased ALT values, (*p<0.05), and no significant infiltration by inflammatory cells (Figure 4d). In the Q-VD-OPH treated animals the liver showed normal histology (Figure 4e) and decreased ALT values (*p<0.05) compared to LV plus Ad-TRAIL injected mice. To assess apoptosis, TUNEL assays were done on all liver samples. In the LV plus Ad-TRAIL infected livers hepatocyte apoptosis was increased (Figure 4d’) compared to only Ad-TRAIL (Figure 4b’) or only LV (Figure 4c’)-injected animals. In the Q-VD-OPH treated animals apoptosis decreased (Figure 4e’). bar=50 μm.