G-CSF administration favours SDF-1 release and activation of neutrophils and monocytes in recipients of autologous peripheral blood progenitor cells

Cytokine. 2019 Apr:116:38-47. doi: 10.1016/j.cyto.2018.12.011. Epub 2019 Jan 24.

Abstract

G-CSF is a growth factor widely used to mobilise CD34+ progenitor cells for clinical applications. The present study aimed to assess expression of G-CSF receptor (CSF3R) on neutrophils and monocytes, as well as SDF-1 and G-CSF serum levels in relation to efficacy of G-CSF-induced mobilisation for autologous transplantation. For this purpose, 105 patients with haematological disorders and 46 healthy controls were investigated. Before mobilisation patients were characterised with significantly higher percentage of CSF3R expressing neutrophils (p < 0.001) and monocytes (p = 0.002), than controls. G-CSF administration resulted in a decrease of CSF3R+ neutrophils (p < 0.001) and monocytes (p < 0.001), while presence of G-CSF receptor on neutrophils tended to negatively affect mobilisation yield (p = 0.075). G-CSF concentration increased during mobilisation (p < 0.001). On the 5th day of mobilisation a positive correlation was observed between G-CSF and SDF-1 serum levels (p < 0.001) and the number of CD34+ cells released from bone marrow seemed to be related to both G-CSF (p = 0.036) and SDF-1 levels (p = 0.084). As compared to Hodgkin's lymphoma patients, those with multiple myeloma had lower basal percentage of CSF3R+ neutrophils (p = 0.014) while Non-Hodgkin's lymphoma cases exhibited higher G-CSF (p = 0.026) and SDF-1 (p = 0.006) concentration on mobilisation day 5. Hodgkin's lymphoma patients were also characterised with worse mobilisation efficacy than multiple myeloma (p = 0.022) and Non-Hodgkin's lymphoma (p = 0.013) patients. These results suggest that both SDF-1 and G-CSF play a role in HSC release into peripheral blood and show that G-CSF administration affects expression of CSF3R on monocytes and neutrophils, implying potential role of these cell subpopulations in mobilisation process.

Keywords: G-CSF/CSF3; HSC transplantation; Monocytes; Neutrophils; SDF-1/CXCL12.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Antigens, CD34 / metabolism
  • Chemokine CXCL12 / blood*
  • Female
  • Granulocyte Colony-Stimulating Factor / blood*
  • Granulocyte Colony-Stimulating Factor / pharmacology*
  • Hematopoietic Stem Cell Mobilization
  • Hematopoietic Stem Cell Transplantation
  • Hematopoietic Stem Cells / metabolism
  • Hodgkin Disease / blood
  • Hodgkin Disease / immunology
  • Humans
  • Male
  • Middle Aged
  • Monocytes / immunology*
  • Multiple Myeloma / blood
  • Multiple Myeloma / immunology
  • Neutrophil Activation / drug effects*
  • Neutrophils / immunology
  • Receptors, Colony-Stimulating Factor / metabolism
  • Transplantation, Autologous
  • Young Adult

Substances

  • Antigens, CD34
  • CSF3R protein, human
  • CXCL12 protein, human
  • Chemokine CXCL12
  • Receptors, Colony-Stimulating Factor
  • Granulocyte Colony-Stimulating Factor