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G-CSF Infusion for Stem Cell Mobilization Transiently Increases Serum Cell-Free DNA and Protease Concentrations
Maria Stoikou1, Shane V van Breda1, Günther Schäfer1
1Department of Biomedicine, University of Basel and University Hospital of Basel, Basel, Switzerland.
Abstract:
G-CSF for stem cell mobilization increases circulating levels of myeloid cells at different stages of maturation. Polymorphonuclear cells (PMNs) are also mobilized in high numbers. It was previously reported that G-CSF primes PMNs toward the release of neutrophils extracellular traps (NETs). Since NETs are often involved in thrombotic events, we hypothesized that high G-CSF blood concentrations could enhance PMN priming toward NET formation in healthy hematopoietic stem cell donors, predisposing them to thrombotic events. However, we found that G-CSF does not prime PMNs toward NETs formation, but increases the serum concentration of cell-free DNA, proteases like neutrophils elastase and myeloperoxidase, and reactive oxygen species. This could possibly create an environment disposed to induce thrombotic events in the presence of additional predisposing factors.
Insights
Granulocyte-colony stimulating factor (G-CSF) mobilization does not prime neutrophils for extracellular trap (NET) formation. However, G-CSF increases factors in the blood that may promote thrombotic events under certain conditions.
Area of Science:
- Hematology
- Immunology
- Thrombosis Research
Background:
- Granulocyte-colony stimulating factor (G-CSF) is used for hematopoietic stem cell mobilization.
- G-CSF increases circulating myeloid cells, including polymorphonuclear cells (PMNs).
- Previous studies suggested G-CSF primes PMNs for neutrophil extracellular trap (NET) release, which is linked to thrombosis.
Purpose of the Study:
- To investigate if G-CSF enhances PMN priming toward NET formation in healthy stem cell donors.
- To determine the effect of high G-CSF concentrations on PMN activation and thrombotic potential.
Main Methods:
- Analysis of circulating myeloid cell populations after G-CSF administration.
- Assessment of PMN priming for NET formation.
- Measurement of serum cell-free DNA, neutrophil elastase, myeloperoxidase, and reactive oxygen species.
Main Results:
- G-CSF did not enhance PMN priming toward NET formation.
- G-CSF significantly increased serum concentrations of cell-free DNA, neutrophil elastase, myeloperoxidase, and reactive oxygen species.
- These changes indicate a pro-thrombotic environment may be created.
Conclusions:
- G-CSF does not directly prime PMNs for NET formation.
- Elevated levels of specific molecules due to G-CSF may contribute to thrombotic events.
- Further research is needed to understand the thrombotic risk associated with G-CSF therapy.
