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Hematopoietic origin of macrophages as studied by chromosome markers in mice
Abstract:
The origin of macrophages was studied in mouse radiation chimeras by chromosome marker technique. Macrophage cultures were established from peritoneal exudate, from lung washings, and from organ cultures of bone marrow, spleen, lymph node, thymus, and lung. Cultured macrophages were induced to divide by adding conditioned medium from L cell cultures. In chimeras which were lethally irradiated and given injections of bone marrow or spleen cells, dividing macrophages were of donor type, independent of the source of the macrophages. When chimeras were established by injections of a mixture of bone marrow cells and cells from other hematopoietic tissues of two genetically different donors, the ratio of cells with different genotypes was approximately the same in bone marrow cells and in macrophage cultures. Thymus, lymph node, and peritoneal exudate cells were not found to contain precursor cells for macrophages. Precursor cells for macrophages and for bone marrow cells appeared to be equally sensitive to sublethal irradiation. The results indicate that macrophages from different sources can all be derived from hematopoietic tissues, and suggest that only hematopoietic tissues contain precursor cells for macrophages which are capable of in vitro division. The close relationship between the source of cells in bone marrow and in macrophage cultures suggests that, at the maturation level at which the irradiated host is repopulated, the precursor or stem cells for macrophages may be identical with those for myeloid and erythroid series of cells.
Insights
Macrophages originate from hematopoietic tissues, not lymph nodes or thymus. Bone marrow and spleen cells contain precursor cells for macrophages, indicating a shared origin with myeloid and erythroid cells.
Area of Science:
- Immunology
- Hematology
- Cell Biology
Background:
- Macrophages are crucial immune cells with diverse tissue origins.
- Understanding macrophage lineage is essential for immunology and regenerative medicine.
Purpose of the Study:
- To investigate the origin and precursor cells of macrophages using mouse radiation chimeras.
- To determine if macrophages from various sources share a common progenitor.
Main Methods:
- Utilized chromosome marker technique in mouse radiation chimeras.
- Established macrophage cultures from peritoneal exudate, lung washings, and organ cultures (bone marrow, spleen, lymph node, thymus, lung).
- Analyzed cell genotypes in chimeras following bone marrow or spleen cell transplantation.
Main Results:
- Dividing macrophages in chimeras were consistently of donor type, regardless of macrophage source.
- Genotype ratios in macrophage cultures mirrored those in bone marrow cells.
- Precursor cells for macrophages were identified in hematopoietic tissues (bone marrow, spleen) but not in thymus, lymph node, or peritoneal exudate.
- Macrophage and bone marrow precursor cells exhibited similar sensitivity to sublethal irradiation.
Conclusions:
- Macrophages from all tested sources are derived from hematopoietic tissues.
- Hematopoietic tissues harbor the sole precursor cells capable of in vitro macrophage division.
- Macrophage stem cells may be identical to those of myeloid and erythroid lineages at the repopulation maturation stage.