期刊
JOURNAL OF LEUKOCYTE BIOLOGY
卷 93, 期 6, 页码 883-893出版社
FEDERATION AMER SOC EXP BIOL
DOI: 10.1189/jlb.1211591
关键词
apoptosis; mTOR; granulocytes; protein kinase B; granulocyte colony-stimulating factor
资金
- Hematology Tissue Bank of the Emory University School of Medicine and the Georgia Cancer Coalition
- National Heart, Lung, and Blood Institute Grant [HL04546-01A2]
- NATIONAL HEART, LUNG, AND BLOOD INSTITUTE [K08HL004546] Funding Source: NIH RePORTER
Neutrophils play an important role in the innate immune response against bacterial and fungal infections. They have a short lifespan in circulation, and their survival can be modulated by several cytokines, including G-CSF. Previous studies have implicated AKT as a critical signaling intermediary in the regulation of neutrophil survival. Our results demonstrate that G-CSF activation of AKT is not sufficient to prolong neutrophil survival. Neutrophils treated with G-CSF undergo apoptosis, even in the presence of high levels of p-AKT. In addition, inhibitors of AKT and downstream targets failed to alter neutrophil survival. In contrast, neutrophil precursors appear to be dependent on AKT signaling pathways for survival, whereas high levels of p-AKT inhibit proliferation. Our data suggest that the AKT/mTOR pathway, although important in G-CSF-driven myeloid differentiation, proliferation, and survival of early hematopoietic progenitors, is less essential in G-CSF suppression of neutrophil apoptosis. Whereas basal AKT levels may be required for the brief life of neutrophils, further p-AKT expression is not able to extend the neutrophil lifespan in the presence of G-CSF.
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