Guinea pig Kupffer cells can be activated in vitro to an enhanced superoxide response. I. Comparison with peritoneal...

Guinea pig Kupffer cells were obtained by partial digestion of the liver with pronase and collagenase and purified by centrifugal elutriation. Cells were kept in monolayer culture and their capacity to secrete superoxide anion in response to phagocytosis of zymosan was determined by the cytochrome c method. Compared to resident peritoneal macrophages, Kupffer cells produced somewhat less superoxide (60% +/- 30%). Both cell types were activated by 24 h preincubation with lipopolysaccharide from Salmonella minnesota or muramyl dipeptide to give twice as high a superoxide response to zymosan. The same effect was achieved when Kupffer cells in vitro were incubated for 3 days with supernatants from phytohaemagglutinin-activated peripheral T lymphocytes or recombinant gamma-interferon. These data demonstrate that the resident macrophages of the liver, the Kupffer cells, are able to increase their capacity to secrete reactive oxygen intermediates after proper activation; this fact is possibly important in the pathogenesis of hepatocyte damage upon inflammatory reactions in the liver.