Immunohistochemical Study of Dendritic Cells and Kupffer Cells in Griseofulvin-Induced Protoporphyric Mice

To determine whether protoporphyric liver injury affects hepatic dendritic cells (DC) and Kupffer cells, we examined liver tissues of griseofulvin-induced protoporphyric mice using histological and immunohistochemical methods. After 1 week of griseofulvin feeding, the protoporphyric liver showed prominent hepatomegaly and a gradual increase in histopathological changes such as hepatocellular hypertrophy, focal necrosis and brown pigment deposits. After 4 weeks of treatment, marked ductular reaction was observed in the liver tissue. Immunohistochemical analyses indicated that the density of NLDC-145-positive hepatic DC gradually decreased during griseofulvin feeding. However, the index of the number of DC in the whole liver appeared to fall sharply after 6 weeks. In contrast, the density of F4/80-positive Kupffer cells gradually increased during griseofulvin feeding. In the spleen and lung, no significant differences were noted in the distribution of NLDC-145-positive DC between experimental and control mice. These results suggested that griseofulvin-induced protoporphyria leads to a specific decrease in the density of hepatic DC due to hepatomegaly until 4 weeks of treatment and is substantial after 6 weeks. This substantial decrease of hepatic DC might have been induced by some alterations in protoporphyric liver injury including ductular reaction at a later stage in this experiment. Since hepatic DC were reduced in number, they seemed to have no significant relation to the progression of griseofulvin-induced protoporphyric liver injury. However, the decrease of hepatic DC might affect the cellular immune response in protoporphyria.