Variation of eicosanoid production by activation of Kupffer cells.

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Since phorbol ester mimics the actions of LPS,we investigated the metabolic alternation by zymosan-pellet after infusion of phorbol 12-myristate 13-acetate (PMA) in the perfused rat livers. PMA-infusion enhanced the production of Tx B_2 and PGD_2 by zymosan-pellet and arachidonic acid.The response of hepatic macrophages and the effects of platelet-activating factor in perfused liver were studied during production of experimental liver cirrhosis induced by thioacetamide in female Sprague-Dawley rats. Within four weeks of thioacetamide administration (300mg/L drinking water) , an increase in hepatic macrophage population and enlargement in cell size preceded the alterations characteristic of cirrhosis. The amount of PGD_2 and TxB_3 in perfusate induced by platelet-activating factor were seven-and five-fold greater, respectively, in thioacetamide-treated than in control rats. Zymosan mimicked the effects of platelet-activating factor. These results are consisted with the hypothesis that hepatic macrophages and platelet-activating factor play important roles in the development cirrhosis induced by thioacetamide.