Experimental Liver Injury Induced by Propionibacterium acnes and Lipopolysaccharide in Macrophage Colony Stimulating Factor-Deficient Osteopetrotic (op/op) Mice

To clarify the involvement of growth anddifferention of liver macrophages mediated by macrophagecolony-stimulating factor (M-CSF) in the liver injuryinduced by Propionibacterium acnes (P. acnes) and lipopolysaccharide (LPS), we usedM-CSF-deficient osteopetrotic (op/op) mice. Seven daysafter injection of P. acnes, granulomas as well as thenumbers of Thy-1.2-, Mac-1-, and ERMP-20-positive cellsand F4/80-positive areas in the liver weresignificantly reduced in the op/op mice compared to thenormal littermates. After injection of LPS, serum levelsof alanine aminotransferase as well as concentrations of IL-1β and TNF-α in the serum andliver were significantly lower in the op/op mice than inthe normal littermates, whereas the concentrations ofIL-1β and TNF-α in the spleen were similar in op/op mice and normal littermates. Theseresults suggest that M-CSF plays a partial but highlysignificant role in the development of liver injuryinduced by P. acnes and LPS via an intrahepatic increase of primed macrophages including those ingranulomas, in response to P. acnes, which produceproinflammatory cytokines such as IL-1β andTNF-α.