| First Author | Souza LR | Year | 2013 |
| Journal | J Leukoc Biol | Volume | 93 |
| Issue | 6 | Pages | 883-93 |
| PubMed ID | 23559492 | Mgi Jnum | J:201281 |
| Mgi Id | MGI:5512926 | Doi | 10.1189/jlb.1211591 |
| Citation | Souza LR, et al. (2013) G-CSF activation of AKT is not sufficient to prolong neutrophil survival. J Leukoc Biol 93(6):883-93 |
| abstractText | 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. |
