G-CSF Infusion for Stem Cell Mobilization Transiently Increases Serum Cell-Free DNA and Protease Concentrations.

Maria Stoikou,Andreas Buser,Laura Infanti,Günther Schäfer,Alexandra Plattner,Shane V Van Breda,Stavros Giaglis,Andreas Holbro,Simona W Rossi,Lenka Vokalova,Sinuhe Hahn

doi:10.3389/fmed.2020.00155

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.

Highlights

Granulocyte colony-stimulating factor (G-CSF) is playing an essential role as a colony-stimulating factor during hematopoiesis
Blood cell counting indicated a striking increase in Polymorphonuclear cells (PMNs)-like cells and PBMCs at the time of apheresis, which returned to control levels 1-month postdonation (Figures 1A,B)
Analysis for the PMN marker CD66b and the stem cell marker CD34 indicated that a high proportion of the PMNs at the time of apheresis were of an early hemopoietic developmental stage (Figure 1C)

Summary

Introduction

Granulocyte colony-stimulating factor (G-CSF) is playing an essential role as a colony-stimulating factor during hematopoiesis. G-CSF stimulates proliferation and differentiation of hematopoietic stem cells (HSC) [1], differentiation of precursor cells into mature PMNs, and the release of mature granulocytes and hematopoietic stem cells from the bone marrow [2]. The latter has led to the widespread use of G-CSF [3] for the mobilization of HSC for transplant purposes [4, 5]. It was described that NETs can promote thrombosis [10] since histones H3 and H4 enhance platelet recruitment by activation of factor XII [11]. NE, MPO and reactive oxygen species (ROS) seem to regulate the clotting cascade and promote coagulation by cleavage and oxidation of anticoagulants; tissue factor pathway

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