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Endotoxin-induced changes in the interrelationship of density subpopulations of granulocyte-macrophage progenitor
Abstract:
Progenitor cells of in vitro colonies of granulocytes and/or macrophages (CFU-s'c) constitute a functionally heterogeneous population reflected by differences in their bouyant density. The interrelationship of density subpopulations of murine (CFU-c, obtained by isopycnic centrifugatiuon of bone marrow cells in continuous albumin density gradients, was examined in perturbed states induced by endotoxin injection. Femoral bone marrow CFU-c's were investigated at daily intervals for 3 days after injection of endotoxin. A distinct difference was found between the changes in CFU-c when detected in vitro with MLCM and HU as the sources of CSF. After 1 day, there was a reduction in the number of CFU-c's, in particular by those CFU-c's of low density (< 1.07 gm/cm3) that are detectable in vitro with CSFMLCM and that form predominantly granulocytic colonies. This was followed on day 2 by the reappearance of this subpopulation. In contrast, those CFU-c's detectable with CSFHU and forming predominantly macrophage colonies were characterized by a high modal density (> 1.075 gm/cm3). Their numbers decreased on day 1, increased by day 2, and further increased above control levels by day 3 when they were characterized by a very high mean modal density of 1.087 gm/cm3. These results indicate that the different types of CSF detect subpopulations of CFU-c's that differ in differentiation potential and perhaps constitute a hierarchy in the myelopoietic pathway.
Insights
Colony-forming cells (CFU-c) in mouse bone marrow show density differences. Endotoxin alters these progenitor cell populations, revealing distinct granulocytic and macrophage precursors in a potential myelopoietic hierarchy.
Area of Science:
- Hematology
- Cell Biology
- Immunology
Background:
- Colony-forming cells (CFU-c) are functionally heterogeneous, differing in buoyant density.
- Understanding CFU-c subpopulations is crucial for studying hematopoiesis and immune responses.
Purpose of the Study:
- To investigate the interrelationship of density subpopulations of murine CFU-c.
- To examine how endotoxin injection perturbs these CFU-c subpopulations.
Main Methods:
- Murine bone marrow cells were subjected to isopycnic centrifugation in continuous albumin density gradients.
- CFU-c subpopulations were analyzed at daily intervals for 3 days post-endotoxin injection.
- Different sources of colony-stimulating factor (CSF), MLCM and HU, were used to detect distinct CFU-c types.
Main Results:
- Endotoxin altered CFU-c populations differently based on density and CSF type.
- Low-density CFU-c (granulocytic precursors) decreased initially and reappeared by day 2.
- High-density CFU-c (macrophage precursors) decreased on day 1, increased by day 2, and further elevated by day 3.
Conclusions:
- Different CSF types detect distinct CFU-c subpopulations with varying differentiation potentials.
- These findings suggest a hierarchy within the myelopoietic pathway.
- Density heterogeneity of CFU-c reflects functional differences and differentiation potential.