| Regulation of steady-state neutrophil homeostasis by macrophages. | |
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MedLine Citation:
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PMID: 20980680 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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-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-1β-independent pathway plays a role in promoting neutrophil production in mice with defective clearance of apoptotic cells. |
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Authors:
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Claire Gordy; Heather Pua; Gregory D Sempowski; You-Wen He |
Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, U.S. Gov't, Non-P.H.S. Date: 2010-10-27 |
Journal Detail:
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Title: Blood Volume: 117 ISSN: 1528-0020 ISO Abbreviation: Blood Publication Date: 2011 Jan |
Date Detail:
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Created Date: 2011-01-14 Completed Date: 2011-02-23 Revised Date: 2012-01-13 |
Medline Journal Info:
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Nlm Unique ID: 7603509 Medline TA: Blood Country: United States |
Other Details:
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Languages: eng Pagination: 618-29 Citation Subset: AIM; IM |
Affiliation:
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Department of Immunology, Duke University Medical Center, Durham, NC, USA. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Bone Marrow Cells / cytology, immunology, metabolism CASP8 and FADD-Like Apoptosis Regulating Protein / deficiency, genetics Cell Survival Gene Knock-In Techniques Granulocyte Colony-Stimulating Factor / metabolism Hematopoiesis / genetics, immunology Homeostasis / genetics, immunology* Inflammation / genetics, immunology Macrophages / immunology*, metabolism Mice Mice, Knockout Neutrophils / immunology*, metabolism Spleen / cytology, immunology, metabolism |
| Grant Support | |
ID/Acronym/Agency:
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AI073947/AI/NIAID NIH HHS; R01 AI073947-04/AI/NIAID NIH HHS; R01 AI073947-05/AI/NIAID NIH HHS; UC6-AI058607/AI/NIAID NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/CASP8 and FADD-Like Apoptosis Regulating Protein; 0/Cflar protein, mouse; 143011-72-7/Granulocyte Colony-Stimulating Factor |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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