Leishmania donovani: in vitro evidence of hepatocyte damage by Kupffer cells and immigrant macrophages in a murine model.

Infection with Leishmania donovani leads to activation of liver macrophages. The role of different macrophage populations of liver in this infection is not clearly defined. Thus, the mechanism involved in hepatocyte damage was studied by coculturing hepatocytes with two populations of liver macrophages, the kupffer cells and immigrant macrophages. The results indicated maximum tissue damage at peak infection in both the macrophage populations cocultured with hepatocytes (P < 0.001). Kupffer cell-hepatocyte coculture treated with scavengers of reactive oxygen intermediates failed to inhibit the hepatocyte damage (P > 0.05). But with heparin and phenylmethylsulfonyl fluoride, a sharp decrease in the damage was noticed (P < 0.001). In contrast, immigrant macrophage-hepatocyte coculture showed a significant reduction in tissue damage when treated with both the scavengers of reactive oxygen intermediates and enzyme inhibitors (P < 0.001). Therefore the murine infection with L. donovani is speculated to involve two distinct subpopulations of liver macrophages with marked differences in morphology and functional capabilities.