Activated liver macrophages in human liver diseases

Immunohistochemical analysis using monoclonal antibodies specific for cells of monocyte/macrophage lineage reveals that resident liver macrophages have a phenotype distinct from that of monocytes or activated liver macrophages. Liver macrophages consist of heterogeneous cell populations in maturation (matured 25F9-positive and immature 25F9-negative) but the ratio of two populations is constant in normal and diseased livers. The expression of CD14 is down-regulated in resident liver macrophages as compared to that in monocytes, while the expression of 25F9 is up-regulated. On the other hand, the expressions of CD14 and Fc gamma RI are up-regulated in activated liver macrophages in viral and autoimmune hepatitis. In vitro culture of monocytes in medium without cytokines induces the phenotype similar to that of resident liver macrophages. Addition of macrophage-colony stimulating factor or interferon-gamma into the culture medium induces the expression of Fc gamma RI, the phenotype of which resembles that of activated liver macrophages. These results suggest that liver macrophages consist of heterogeneous cell populations and that both phenotype and function are affected by the local milieu of cytokines.