Guinea pig Kupffer cells can be activated in vitro to an enhanced superoxide response. II. Involvement of eicosanoids.
In the preceding paper it was shown that Kupffer cells isolated by digestion of the liver and purified by centrifugal elutriation can be activated in vitro by lipopolysaccharide and muramyl dipeptide to an enhanced superoxide response upon zymosan phagocytosis. Lipopolysaccharide and muramyl dipeptide also led to a strongly increased prostaglandin E2 release during the phagocytosis of zymosan. This activation was accompanied by an increased production of prostaglandin E2 during the incubation with the stimuli. Prostaglandin E2 synthesis was inhibited by the cyclooxygenase inhibitor indomethacin, reduced by dexamethasone, but only slightly decreased by the lipoxygenase inhibitor nordihydroguaiaretic acid. Indomethacin and dexamethasone also reduced the superoxide response, which only in the case of indomethacin is reversed by exogenous prostaglandin E2. Dexamethasone reduced the superoxide response in unstimulated cells as well. From these results it is deduced that cyclo-oxygenase products, especially prostaglandin E2, but not lipoxygenase products, i.e. leukotrienes, play some regulatory role in the activation process of Kupffer cells; in addition, a prostaglandin-independent inhibition exerted by dexamethasone seems to exist.
Rieder
H
H
I. Medizinische Klinik, Johannes Gutenberg-Universität, Mainz, F.R.G.
Ramadori
G
G
Meyer zum Büschenfelde
K H
KH
D000119:Acetylmuramyl-Alanyl-Isoglutamine / Q000494:pharmacology; D000818:Animals; D002478:Cells, Cultured; D005260:Female; D006168:Guinea Pigs; D007213:Indomethacin / Q000494:pharmacology; D007728:Kupffer Cells / Q000187:drug effects / Q000502:physiology*; D008070:Lipopolysaccharides / Q000494:pharmacology; D011453:Prostaglandins / Q000096:biosynthesis / Q000502:physiology*; D012016:Reference Values; D013481:Superoxides / Q000378:metabolism*
D008070:Lipopolysaccharides; D011453:Prostaglandins; D013481:Superoxides; D000119:Acetylmuramyl-Alanyl-Isoglutamine; D007213:Indomethacin