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Mature and immature myeloid cells decrease the granulocyte colony-stimulating factor level by absorption of
1Third Department of Internal Medicine, Dokkyo University School of Medicine, Tochigi, Japan.
Abstract:
We studied the effects of polymorphonuclear neutrophils (PMN) and immature myeloid cells on the granulocyte colony-stimulating factor (G-CSF) level in vitro to better understand the regulatory mechanisms of neutropoiesis. Intact normal PMN decreased the G-CSF level after incubation with recombinant human (rh) G-CSF in a time- and dose-dependent manner. The percent reduction decreased as the concentration of rhG-CSF increased. However, the cell-free PMN-conditioned medium (PMN-CM) did not decrease the G-CSF level. The intact PMN also decreased the granulocyte-macrophage (GM)-CSF level after culture with rhGM-CSF, but did not affect the monocyte (M)-CSF level after culture with rhM-CSF. Normal bone marrow (BM) immature neutrophilic cells and G-CSF-dependent acute myeloid leukemic cells (OCI/AML la) also decreased the G-CSF level, whereas K-562 cells, which have no detectable G-CSF receptors, did not affect it. Phenylarsine oxide (PhAsO), an inhibitor of endocytosis of ligand receptor complex, abrogated this decreasing effect of intact PMN and OCI/AML la cells. These findings suggest that mature and immature myeloid cells negatively regulate neutropoiesis by, at least in part, decreasing the G-CSF level probably through receptor-mediated continual absorption and metabolism of G-CSF.
Insights
Mature and immature myeloid cells reduce granulocyte colony-stimulating factor (G-CSF) levels, suggesting a negative feedback loop in neutropoiesis. This occurs through cellular absorption and metabolism of G-CSF.
Area of Science:
- Hematology
- Cell Biology
- Immunology
Background:
- Neutropoiesis, the production of neutrophils, is a tightly regulated process.
- Granulocyte colony-stimulating factor (G-CSF) is a key cytokine in regulating neutrophil production.
- Understanding the feedback mechanisms controlling G-CSF levels is crucial for comprehending neutropoiesis regulation.
Purpose of the Study:
- To investigate the in vitro effects of polymorphonuclear neutrophils (PMN) and immature myeloid cells on G-CSF levels.
- To elucidate the regulatory mechanisms of neutropoiesis involving G-CSF.
Main Methods:
- Incubation of recombinant human (rh) G-CSF with intact normal PMN and observed time- and dose-dependent effects.
- Assessed the impact of cell-free PMN-conditioned medium (PMN-CM) on G-CSF levels.
- Evaluated the effects of normal bone marrow (BM) immature neutrophilic cells and leukemic cell lines (OCI/AML la, K-562) on G-CSF levels.
- Utilized phenylarsine oxide (PhAsO) to inhibit endocytosis and assess its effect on G-CSF level reduction.
Main Results:
- Intact PMN significantly decreased G-CSF levels in a time- and dose-dependent manner, with reduced effect at higher G-CSF concentrations.
- PMN-CM did not affect G-CSF levels, indicating direct cell-cell contact or intact cell involvement.
- Intact PMN reduced granulocyte-macrophage (GM)-CSF but not monocyte (M)-CSF levels.
- Immature myeloid cells and G-CSF-dependent leukemic cells reduced G-CSF levels, while cells lacking G-CSF receptors did not.
- Phenylarsine oxide (PhAsO) abrogated the G-CSF-decreasing effect of PMN and leukemic cells, suggesting receptor-mediated endocytosis.
Conclusions:
- Mature and immature myeloid cells negatively regulate neutropoiesis by decreasing G-CSF levels.
- This regulation likely occurs through receptor-mediated continuous absorption and metabolism of G-CSF.
- Findings highlight a novel negative feedback mechanism in the control of neutrophil production.