Seiji Morisawa

Possible induction of fatty acid cyclo-oxygenase in lipopolysaccharide-stimulated rat Kupffer cells

In response to stimulation with lipopolysaccharide, isolated rat Kupffer cells released increased amounts of prostaglandin E2, prostaglandin D2, 6-keto-prostaglandin F1 alpha, and thromboxane B2. There was a lag of 2-6 hours before a significant release of these metabolites into the medium was detected. Nonstimulated Kupffer cells converted exogenous arachidonic acid to prostaglandins and thromboxane B2, and a major product was prostaglandin D2. Twenty-four hours after stimulation with lipopolysaccharide, Kupffer cells produced approximately 7 times more prostaglandin E2 and 2 times more prostaglandin D2, 6-keto-prostaglandin F1 alpha; and thromboxane B2 than nonstimulated cells. Western immunoblotting of microsomal proteins prepared from the stimulated rat Kupffer cells showed a 70-kilodalton component that was immunoreactive with a polyclonal anticyclo-oxygenase antibody. The intensity of the band increased with the time of the lipopolysaccharide stimulation. These results suggest that the accelerated arachidonate metabolism in lipopolysaccharide-stimulated rat Kupffer cells might be attributed to an induction of the cyclo-oxygenase enzyme.

Changes in prostaglandins and leukotrienes in the liver tissue of guinea pigs in the experimental massive hepatic cell necrosis model.

When trinitrophenylated hepatocytes and lipopolysaccharide are intravenously injected into trinitrophenylated liver protein sensitized guinea pigs, most of the guinea pigs die of massive hepatic cell necrosis within 24 hours of LPS injection. Using this experimental model, we studied the changes in the levels of leukotrienes (LTs) and prostaglandins (PGs) in the liver tissue of guinea pigs with experimentally-induced massive hepatic cell necrosis. As a result, both the levels of LTs and PGs in the liver tissue increased. These results suggest that the arachidonic acid metabolites may play an important role in the induction of liver cell injury.