title: Autophagy is required for stem cell mobilization by G-CSF.
abstract: Granulocyte colony-stimulating factor (G-CSF) is widely used clinically to prevent neutropenia after cytotoxic chemotherapy and to mobilize hematopoietic stem cells (HSCs) for transplantation. Autophagy, a process of cytoplasmic component recycling, maintains cellular homeostasis and protects the cell during periods of metabolic stress or nutrient deprivation. We have observed that G-CSF activates autophagy in neutrophils and HSCs from both mouse and human donors. Furthermore, G-CSF-induced neutrophil and HSC mobilization is impaired in the absence of autophagy. In contrast, autophagy is dispensable for direct HSC mobilization in response to the CXCR4 antagonist AMD3100. Altogether, these data demonstrate an important role for G-CSF in invoking autophagy within hematopoietic and myeloid cells and suggest that this pathway is critical for ensuring cell survival in response to clinically relevant cytokine-induced stress. These findings have direct relevance to HSC transplantation and the increasing clinical use of agents that modulate autophagy.
authors: Division of Immunology, QIMR Berghofer Medical Research Institute, Herston, Queensland, Australia; School of Medicine, The University of Queensland, Brisbane, Queensland, Australia;
authors: Lucie
authors: L
authors: Leveque-El Mouttie
authors: Division of Immunology, QIMR Berghofer Medical Research Institute, Herston, Queensland, Australia; School of Medicine, The University of Queensland, Brisbane, Queensland, Australia;
authors: Therese
authors: T
authors: Vu
authors: Division of Immunology, QIMR Berghofer Medical Research Institute, Herston, Queensland, Australia; School of Medicine, The University of Queensland, Brisbane, Queensland, Australia;
authors: Katie E
authors: KE
authors: Lineburg
authors: Division of Immunology, QIMR Berghofer Medical Research Institute, Herston, Queensland, Australia;
authors: Rachel D
authors: RD
authors: Kuns
authors: Finsen Laboratory, Bioinformatics Centre, Department of Biology, and Biotech Research and Innovation Center, University of Copenhagen, Denmark;
authors: Frederik O
authors: FO
authors: Bagger
authors: Division of Immunology, QIMR Berghofer Medical Research Institute, Herston, Queensland, Australia;
authors: Bianca E
authors: BE
authors: Teal
authors: Division of Immunology, QIMR Berghofer Medical Research Institute, Herston, Queensland, Australia;
authors: Mary
authors: M
authors: Lor
authors: Division of Immunology, QIMR Berghofer Medical Research Institute, Herston, Queensland, Australia;
authors: Glen M
authors: GM
authors: Boyle
authors: Division of Immunology, QIMR Berghofer Medical Research Institute, Herston, Queensland, Australia;
authors: Claudia
authors: C
authors: Bruedigam
authors: Department of Biochemistry and Molecular Biology, Bio21 Molecular Science and Biotechnology Institute, The University of Melbourne, Parkville, Australia; and.
authors: Justine D
authors: JD
authors: Mintern
authors: Division of Immunology, QIMR Berghofer Medical Research Institute, Herston, Queensland, Australia; School of Medicine, The University of Queensland, Brisbane, Queensland, Australia; Department of Haematology, Royal Brisbane and Women's Hospital, Brisbane, Australia.
authors: Geoffrey R
authors: GR
authors: Hill
authors: Division of Immunology, QIMR Berghofer Medical Research Institute, Herston, Queensland, Australia;
authors: Kelli P A
authors: KP
authors: MacDonald
authors: Division of Immunology, QIMR Berghofer Medical Research Institute, Herston, Queensland, Australia; School of Medicine, The University of Queensland, Brisbane, Queensland, Australia; Department of Haematology, Royal Brisbane and Women's Hospital, Brisbane, Australia.
authors: Steven W
authors: http://orcid.org/0000-0002-8050-6209
authors: SW
authors: Lane
mesh_terms: D000818:Animals; D019380:Anti-HIV Agents / Q000494:pharmacology; D018952:Antigens, CD34 / Q000235:genetics / Q000378:metabolism; D001343:Autophagy; D000071187:Autophagy-Related Protein 5; D001596:Benzylamines; D015153:Blotting, Western; D002478:Cells, Cultured; D000080027:Cyclams; D005434:Flow Cytometry; D016179:Granulocyte Colony-Stimulating Factor / Q000494:pharmacology*; D019650:Hematopoietic Stem Cell Mobilization; D018380:Hematopoietic Stem Cell Transplantation; D006412:Hematopoietic Stem Cells / Q000187:drug effects* / Q000473:pathology; D006571:Heterocyclic Compounds / Q000494:pharmacology; D006801:Humans; D051379:Mice; D018345:Mice, Knockout; D008869:Microtubule-Associated Proteins / Q000502:physiology; D009504:Neutrophils / Q000187:drug effects / Q000473:pathology; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D019718:Receptors, CXCR4 / Q000037:antagonists & inhibitors; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014182:Transplantation, Autologous
chemical_list: D019380:Anti-HIV Agents; D018952:Antigens, CD34; C495773:Atg5 protein, mouse; D000071187:Autophagy-Related Protein 5; D001596:Benzylamines; D000080027:Cyclams; D006571:Heterocyclic Compounds; D008869:Microtubule-Associated Proteins; D012333:RNA, Messenger; D019718:Receptors, CXCR4; D016179:Granulocyte Colony-Stimulating Factor; C088327:plerixafor