Expansion of bone marrow neutrophils following G-CSF administration in mice results in osteolineage cell apoptosis and mobilization of hematopoietic stem and progenitor cells

P. Singh, P. Hu, J. Hoggatt, A. Moh, L. M. Pelus

Research output: Contribution to journalArticle

33 Scopus citations

Abstract

Proliferation and differentiation of hematopoietic stem/progenitor cells (HSPC) within bone marrow (BM) niches are regulated by adhesion molecules and cytokines produced by mesenchymal stem/progenitor cells (MPC) and osteoblasts (OB). HSPCs that egresses to peripheral blood are widely used for transplant and granulocyte-colony stimulating factor (G-CSF) is used clinically to induce mobilization. The mechanisms, through which G-CSF regulates HSPC trafficking, however, are not completely unDerstood. Herein we show that G-CSF-driven neutrophil expansion alters the BM niche that leads to HSPC mobilization. Alcam Sca-1 MPC and Alcam Sca-1 OB are reduced coincident with mobilization, which correlates inversely with BM neutrophil expansion. In mice made neutropenic by the neutrophil-specific anti-Ly6G antibody, G-CSF-mediated reduction in MPC and OB is attenuated and mobilization reduced without an effect on monocytes/macrophages. Neutrophils, expanded in response to G-CSF-induced MPC and OB apoptosis leading to reduced production of BM HSPC retention factors, including stromal cell-Derived factor-1, stem cell factor and vascular cell adhesion molecule-1. Blockade of neutrophil reactive oxygen species attenuates G-CSF-mediated MPC and OB apoptosis. These data show that the expansion of BM neutrophils by G-CSF contributes to the transient degradation of retention mechanisms within the BM niche, facilitating enhanced HSPC egress/mobilization.

Original languageEnglish (US)
Pages (from-to)2375-2383
Number of pages9
JournalLeukemia
Volume26
Issue number11
DOIs
StatePublished - Nov 1 2012

Keywords

  • G-CSF
  • Hematopoietic niche disruption and ROS
  • HSPC mobilization
  • Neutrophil expansion
  • Osteolineage cells

ASJC Scopus subject areas

  • Hematology
  • Cancer Research
  • Anesthesiology and Pain Medicine

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