Autophagy is required for stem cell mobilization by G-CSF
Autophagy is required for stem cell mobilization by G-CSF
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DOI：
10.1182/blood-2014-03-562660
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发表时间：
2015-05-07
期刊：
影响因子：
20.3
通讯作者：
Lane, Steven W.
中科院分区：
文献类型：
--
作者：
Leveque-El Mouttie, Lucie;Vu, Therese;Lane, Steven W.
粒细胞集落刺激因子（G-CSF）在临床上广泛用于预防细胞毒性化疗后的中性粒细胞减少和动员造血干细胞（hsc）进行移植。自噬是一种细胞质成分循环的过程，在代谢应激或营养剥夺期间维持细胞稳态并保护细胞。我们观察到G-CSF激活小鼠和人类供体中性粒细胞和造血干细胞的自噬。此外，在没有自噬的情况下，g - csf诱导的中性粒细胞和HSC动员受到损害。相比之下，在对CXCR4拮抗剂AMD3100的反应中，自噬对于直接动员HSC是不可缺少的。总之，这些数据证明了G-CSF在造血细胞和髓细胞内激活自噬方面的重要作用，并表明该途径对于确保细胞在临床相关细胞因子诱导的应激反应中存活至关重要。这些发现与造血干细胞移植和越来越多的临床使用调节自噬的药物直接相关。
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.