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In order to verify whether rat hepatocytes are capable of producing leukotrienes, Percoll density gradient centrifugation to fractionize rat hepatocytes and a radioimmunoassay of leukotrienes in the reacting solution have been performed. Also, investigated was effect of retinol (Vitamin A) on inducing the production of leukotrienes in rat Kupffer cells and hepatocytes. Incubation with endotoxin (10 micrograms/ml) for 30-60 minutes induced the production of leukotrienes in rat Kupffer cells but did not induce any such production in rat hepatocytes. On the other hand, arachidonic acid (2-20 microM) or linoleic acid (10-50 microns) did induce hepatocytes to produce leukotrienes in a dose-dependent manner. Fifteen minutes of pre-incubation with 10(-8) M of retinol inhibited an endotoxic induction of leukotrienes production in rat Kupffer cells, whereas it did not inhibit an arachidonic acid induction in rat hepatocytes. Based on these results, we have concluded that a hepatic tissue injury during sepsis is probably mediated by leukotrienes produced by the Kupffer cells and its inhibition is the mechanism of tissue protective effect of retinol. However, in further severe state even the hepatocytes may produce leukotrienes and as a consequence, a widespread destruction of hepatic tissue will occur.
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