The effect of prostaglandins E1 and E2 on macrophage progenitor cells with high proliferative potential in mouse bone
Abstract:
High proliferative potential macrophage progenitor cells (HPP-CFC) in 5-fluorouracil (FU) treated and normal mouse bone marrow (BM) have been shown to be less sensitive to inhibition of proliferation by prostaglandins of the E series (PGE) than low proliferative potential macrophage progenitor cells (LPP-CFC) in normal BM in agar cultures. The growth of large colonies (diameter greater than 0.5 mm) derived from HPP-CFC in FU BM, which require a combination of macrophage colony-stimulating factor (CSF-1) plus a new growth factor called synergistic activity (SA), are inhibited by 50% in the presence of 5.5 X 10(-6) M PGE1. On the other hand, LPP-CFC in normal BM, which form smaller colonies (diameter less than or equal to 0.5 mm) in the presence of CSF-1 alone, require only 5 X 10(-8) M PGE1 for the same level of inhibition. Addition of appropriate concentrations of PGE1 to the agar culture assay should improve detection of HPP-CFC by inhibiting the proliferation of LPP-CFC. These observations suggest that the apparent negative feedback control of macrophage production by PGE operates largely on the LPP-CFC, which respond to CSF-1 alone, and is probably not involved in the regulation of the more primitive HPP-CFC.
Insights
Prostaglandins of the E series (PGE) inhibit macrophage progenitor cells. Lower concentrations of PGE inhibit low proliferative potential macrophage progenitor cells (LPP-CFC) more effectively than high proliferative potential macrophage progenitor cells (HPP-CFC).
Area of Science:
- Hematopoiesis
- Cell Biology
- Immunology
Background:
- Macrophage production is regulated by negative feedback mechanisms.
- Prostaglandins of the E series (PGE) are implicated in this regulation.
- Differentiation of macrophage progenitor cells involves distinct proliferative potentials.
Purpose of the Study:
- To investigate the differential sensitivity of macrophage progenitor cells to PGE.
- To explore the role of PGE in regulating macrophage production.
- To optimize the detection of high proliferative potential macrophage progenitor cells (HPP-CFC).
Main Methods:
- Agar culture assays were used to culture mouse bone marrow cells.
- Cells were treated with 5-fluorouracil (FU) to isolate progenitor populations.
- Proliferation of HPP-CFC and LPP-CFC was assessed in the presence of macrophage colony-stimulating factor (CSF-1), synergistic activity (SA), and varying concentrations of PGE1.
Main Results:
- HPP-CFC from FU-treated bone marrow showed less sensitivity to PGE1 inhibition compared to LPP-CFC from normal bone marrow.
- A 50% inhibition of HPP-CFC growth required 5.5 X 10(-6) M PGE1, while LPP-CFC required only 5 X 10(-8) M PGE1.
- Addition of PGE1 to agar cultures enhanced the detection of HPP-CFC by inhibiting LPP-CFC proliferation.
Conclusions:
- PGE-mediated negative feedback on macrophage production primarily affects LPP-CFC.
- The more primitive HPP-CFC appear to be less involved in PGE-regulated macrophage production.
- PGE1 can be utilized to improve the selective detection and study of HPP-CFC.
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