Fig. 1.

Dynamic interactions between parenchymal and non-parenchymal cells in the liver during the progression of ALD. Parenchymal cells/hepatocytes carry out the primary metabolic functions of the liver. One particularly important function of hepatocytes is to metabolize ethanol. In the context of chronic ethanol exposure, expression of CYP2E1 is increased in hepatocytes and Kupffer cells. Ethanol metabolism via this pathway increases redox stress within the liver, resulting in a condition of “organelle stress” whereby the hepatocytes exhibit impaired metabolic function. Although hepatocytes are the most abundant cell type in the liver, normal physiologic function depends on interaction between hepatocytes and non-parenchymal cells (NPCs). NPCs include liver sinusoidal endothelial cells, natural killer cells, natural killer T cells, and Kupffer cells, the liver resident macrophage. Kupffer cells are an important site for the production of inflammatory mediators, such as TNFα, during ethanol exposure. Kupffer cells and hepatocytes are also important sources of chemokines, such as MCP-1 and MIF, which serve to recruit peripheral leukocytes to the liver in response to hepatocellular injury and inflammation.