Scheme of the role of Kupffer cells during Pb(NO3)2-induced hepatic apoptosis. Pb(NO3)2 particles induce, as an early event, Kupffer cells (KC) to secrete molecules (probably cytokines such as TNF alpha) which stimulate hepatocytes (HEP) to proliferate; the increased level of secreted molecules could initiate hepatocyte apoptosis. Activated Kupffer cells may release other molecules prompting endothelial cells (EC) to release additional cytokines, promoting apoptosis of hepatocytes. At the same time, EC can release cytokines that could promote hepatocyte apoptosis as well as activation of KC. As a late event, Pb(NO3)2 particles induce KC death. GdCl3 particles could inhibit the effects of Pb(NO3)2 by depleting Kupffer cells, likely by inducing apoptosis.