Potential role of Kupffer cells in initiating liver injury during endotoxemia.

The potential contribution of Kupffer cells (KCs) to endotoxin-induced liver damage was evaluated by measuring the functional changes of KGs [Superoxide (O2-) generation, and chemotaxis (CTx)] isolated from such livers and comparing them with biochemical and histological changes of liver damage. Sublethal doses of endotoxin was daily administered to rats for 4 days. Liver damage was apparent in the rats treated with single administration of endotoxin and the maximal change was observed in the rats treated with endotoxin for 2 days in association with the marked enhancement of O2- release and CTx in vitro by KCs from these animals. However, liver injury decreased in the rats treated with endotoxin for 3 days and the rats treated with endotoxin for 4 days had shown almost no detectable injury. KCs' biological functions also diminished in group treated for 3 and 4 days. In particular, oxidative and chemotactic responses of KCs from rats treated for 4 days significantly decreased, compared with the cells from those treated for only two days. These results indicate that KCs are pivotal in the pathogenesis of liver injury during endotoxemia.