Autophagy is required for stem cell mobilization by G-CSF

作者：Leveque El Mouttie Lucie; Vu Therese; Lineburg Katie E; Kuns Rachel D; Bagger Frederik O; Teal Bianca E; Lor Mary; Boyle Glen M; Bruedigam Claudia; Mintern Justine D; Hill Geoffrey R; MacDonald Kelli P A^*; Lane Steven W

来源：Blood, 2015, 125(19): 2933-2936.

DOI：10.1182/blood-2014-03-562660

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.

• 出版日期2015-5-7