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Activated liver macrophages in human liver diseases
K Yamamoto1, M Ohmoto, S Matsumoto
1First Department of Internal Medicine, Okayama University Medical School, Japan.
Abstract:
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.
Insights
Resident liver macrophages exhibit distinct phenotypes from monocytes and activated macrophages, with a consistent ratio of immature and mature cells. Cytokines influence macrophage phenotype and function in the liver.
Area of Science:
- Immunology
- Hepatology
- Cell Biology
Background:
- Liver macrophages, crucial for immune surveillance and homeostasis, display diverse phenotypes.
- Understanding resident liver macrophage heterogeneity is key to comprehending liver immunity and disease pathogenesis.
Purpose of the Study:
- To characterize the distinct phenotypes of resident liver macrophages compared to monocytes and activated liver macrophages.
- To investigate the heterogeneity of resident liver macrophages based on maturation status.
- To explore the influence of cytokines on liver macrophage phenotype and function.
Main Methods:
- Immunohistochemical analysis using monoclonal antibodies specific for monocyte/macrophage lineage cells.
- Phenotypic characterization of resident, immature, mature, and activated liver macrophages.
- In vitro culture of monocytes with varying cytokine conditions (e.g., macrophage-colony stimulating factor, interferon-gamma).
Main Results:
- Resident liver macrophages possess a unique phenotype, distinct from monocytes and activated macrophages, characterized by down-regulated CD14 and up-regulated 25F9 expression.
- Liver macrophages comprise heterogeneous populations (25F9-positive mature and 25F9-negative immature), with a stable ratio in normal and diseased livers.
- Activated liver macrophages in viral and autoimmune hepatitis show up-regulated CD14 and Fc gamma RI expression.
- In vitro culture of monocytes without cytokines yielded a phenotype similar to resident liver macrophages.
- Addition of macrophage-colony stimulating factor or interferon-gamma induced Fc gamma RI expression, resembling activated liver macrophages.
Conclusions:
- Liver macrophages are heterogeneous, with distinct populations based on maturation.
- The local cytokine environment significantly influences the phenotype and function of liver macrophages.
- These findings provide insights into liver macrophage biology and their role in hepatic inflammation and disease.