Figure 6.

Implication of platelate-activating factor, ET-1, Kupffer cells and hepatic stellates cells in the pathology of liver cirrhosis. Increased ET-1 released by stellates and endothelial cells in the cirrhosis liver acts on upregulated ET_B receptors in Kupffer cells and stimulates the synthesis of PAF. Likewise, autocrine actions of proinflammatory mediator such as IL-1 and TNF-α may also stimulate PAF synthesis by Kupffer cells. PAF then acts on hepatic vascular smooth muscle cells and stellate cells and contributes to portal hypertension by causing their contraction. Its spillover into systemic circulation is likely a cause of hypertension associated with cirrhosis. Autocrine PAF and paracrine ET-1 can act on their respective upregulated receptors in Kupffer cells and stellate cells to cause the synthesis and release of prostaglandin E₂, which in turn may act to limit the liver injury.