Regulation of fibroblast proliferation by Kupffer cells and monocytes

Liver cirrhosis can be considered as an alteration of the homeostatic mechanisms that maintain cell-cell and cell-matrix interactions. The mechanisms that maintain homeostasis and, therefore, that control fibroblast proliferation and collagen synthesis, are unknown. Experiments were performed to study the role of Kupffer cells in regulating fibroblast proliferation and collagen synthesis and to study the antifibrogenic properties of colchicine. Non-parenchymal cells isolated from normal and CCl4-treated rats were cultured. The cultures from normal livers contained few fibroblasts whereas those from CCl4-treated animals contained many fibroblasts. Removal of adherent cells obtained from normal liver favoured fibroblast proliferation. The fibroblasts from normal or CCl4-treated rats were similar and contained collagens type I and type III. The results obtained suggest that normal Kupffer cells control fibroblast proliferation and that incoming monocytes stimulate fibroblast proliferation. Colchicine inhibits the entry of monocytes into the injured liver and could prevent liver fibrosis by this mechanism.