Direct evidence of macrophage differentiation from bone marrow cells in the liver: a possible origin of Kupffer cells
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Updated: Oct 3, 2026
A Simple and Efficient Method to Isolate Macrophages from Mixed Primary Cultures of Adult Liver Cells
Published on: May 24, 2011
R Takezawa1, Y Watanabe, T Akaike
1Department of Biomolecular Engineering, Tokyo Institute of Technology, Yokohama.
Abstract:
Controversy has surrounded origin and differentiation of tissue macrophages. We directly demonstrate the differentiation of bone marrow cells into macrophages in the liver in vivo using a cell-labeling fluorescence dye, PKH-26. Bone marrow cells labeled with PKH26 were intravenously injected into syngenic mice, and these cells were tracked by flow cytometric analysis. The majority of the labeled cells were detected only in the liver after 4 days. Interestingly, antigens specific for macrophage lineage cells (F4/80, Fc gamma RII, and CD14) were detected on the liver-accumulated cells only 4 h after the injection. The pattern of the antigen expression changed to that of Kupffer cells (F4/80+, Fc gamma RII+, Mac-1-) after 4 days and remained so thereafter. These labeled cells in the liver were esterase staining-positive and showed phagocytic activity at day 7. The number of labeled cells among the Kupffer cells in the liver increased with days after injection. This indicates that bone marrow cells accumulate in the liver and differentiate into liver macrophages on site. Roles of factors secreted from hepatocytes are also discussed.
Insights
Bone marrow cells can transform into liver macrophages directly within the liver. This study tracks labeled bone marrow cells, confirming their differentiation into Kupffer cells in vivo.
Area of Science:
- Immunology
- Cell Biology
- Hematology
Background:
- The origin and differentiation of tissue macrophages, particularly liver macrophages (Kupffer cells), have been a subject of ongoing scientific debate.
- Understanding macrophage origins is crucial for regenerative medicine and treating inflammatory liver diseases.
Purpose of the Study:
- To directly demonstrate the in vivo differentiation of bone marrow-derived cells into functional liver macrophages.
- To elucidate the kinetics and phenotypic changes during this differentiation process.
Main Methods:
- Utilized PKH-26, a cell-labeling fluorescent dye, to track bone marrow cells injected intravenously into syngenic mice.
- Employed flow cytometric analysis to detect labeled cells and assess macrophage lineage-specific antigen expression (F4/80, Fc gamma RII, CD14).
- Evaluated esterase staining and phagocytic activity to confirm macrophage function.
Main Results:
- PKH-26 labeled bone marrow cells predominantly accumulated in the liver within 4 days post-injection.
- Liver-accumulated cells rapidly acquired macrophage lineage markers (4 hours) and subsequently differentiated into Kupffer cells (4 days).
- Differentiated cells exhibited esterase positivity and phagocytic activity, confirming their functional macrophage status.
Conclusions:
- Bone marrow cells migrate to the liver and differentiate on-site into Kupffer cells, resolving controversy about their origin.
- This study provides direct in vivo evidence for bone marrow-derived macrophage differentiation in the liver.
- The findings suggest that hepatocyte-secreted factors may play a role in regulating this differentiation process.
