ABSTRACT
The author is interested in studying the potential role of activated macrophages and endothelial cells in hepatotoxicity. He finds that treatment of rats with hepatotoxic doses of acetaminophen or lipopolysaccharide results in a significant increase in the number of macrophages and endothelial cells in the liver. These cells are known to release reactive mediators which may be inflammatory, cytotoxic, and/or vasoactive and have been implicated in liver injury. When animals are treated with agents that activate hepatic macrophages and endothelial cells, such as lipopolysaccharide or poly I:C, acetaminophen hepatotoxicity is enhanced. In contrast, a hepatoprotective effect is observed following treatment of animals with gadolinium chloride or dextran sulfate, which block Kupffer cell function. Thus, in this example, macrophages and endothelial cells appear to play a critical role in liver parenchymal cell damage. The chapter summarizes the author's experimental data implicating these hepatic nonparenchymal cells in the toxicity of lipopolysaccharide and acetaminophen.
