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- Claire Gordy
- Department of Immunology and
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- Heather Pua
- Department of Immunology and
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- Gregory D. Sempowski
- Departments of Medicine and Pathology and the Human Vaccine Institute, Duke University Medical Center, Durham, NC
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- You-Wen He
- Department of Immunology and
抄録
<jats:title>Abstract</jats:title><jats:p>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-1β, but not IL-17. c-FLIPf/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-1β–independent pathway plays a role in promoting neutrophil production in mice with defective clearance of apoptotic cells.</jats:p>
収録刊行物
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- Blood
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Blood 117 (2), 618-629, 2011-01-13
American Society of Hematology