| First Author | Gordy C | Year | 2011 |
| Journal | Blood | Volume | 117 |
| Issue | 2 | Pages | 618-29 |
| PubMed ID | 20980680 | Mgi Jnum | J:168403 |
| Mgi Id | MGI:4888165 | Doi | 10.1182/blood-2010-01-265959 |
| Citation | Gordy C, et al. (2011) Regulation of steady-state neutrophil homeostasis by macrophages. Blood 117(2):618-29 |
| abstractText | The timely clearance of apoptotic neutrophils from inflammation sites is an important function of macrophages; however, the role of macrophages in maintaining neutrophil homeostasis under steady-state conditions is less well understood. By conditionally deleting the antiapoptotic gene cellular FLICE-like inhibitory protein (C-FLIP) in myeloid cells, we have generated a novel mouse model deficient in marginal zone and bone marrow stromal macrophages. These mice develop severe neutrophilia, splenomegaly, extramedullary hematopoiesis, decreased body weight, and increased production of granulocyte colony-stimulating factor (G-CSF) and IL-1beta, but not IL-17. c-FLIP(f/f) LysM-Cre mice exhibit delayed clearance of circulating neutrophils, suggesting that failure of macrophages to efficiently clear apoptotic neutrophils causes production of cytokines that drive excess granulopoiesis. Further, blocking G-CSF but not IL-1R signaling in vivo rescues this neutrophilia, suggesting that a G-CSF-dependent, IL-1beta-independent pathway plays a role in promoting neutrophil production in mice with defective clearance of apoptotic cells. |
