Journal article
Expression of the G-CSF receptor in monocytic cells is sufficient to mediate hematopoietic progenitor mobilization by G-CSF in mice
The Journal of experimental medicine, Vol.208(2), pp.251-260
02/14/2011
DOI: 10.1084/jem.20101700
PMCID: PMC3039862
PMID: 21282380
Abstract
Granulocyte colony-stimulating factor (G-CSF), the prototypical mobilizing cytokine, induces hematopoietic stem and progenitor cell (HSPC) mobilization from the bone marrow in a cell-nonautonomous fashion. This process is mediated, in part, through suppression of osteoblasts and disruption of CXCR4/CXCL12 signaling. The cellular targets of G-CSF that initiate the mobilization cascade have not been identified. We use mixed G-CSF receptor (G-CSFR)-deficient bone marrow chimeras to show that G-CSF-induced mobilization of HSPCs correlates poorly with the number of wild-type neutrophils. We generated transgenic mice in which expression of the G-CSFR is restricted to cells of the monocytic lineage. G-CSF-induced HSPC mobilization, osteoblast suppression, and inhibition of CXCL12 expression in the bone marrow of these transgenic mice are intact, demonstrating that G-CSFR signals in monocytic cells are sufficient to induce HSPC mobilization. Moreover, G-CSF treatment of wild-type mice is associated with marked loss of monocytic cells in the bone marrow. Finally, we show that bone marrow macrophages produce factors that support the growth and/or survival of osteoblasts in vitro. Together, these data suggest a model in which G-CSFR signals in bone marrow monocytic cells inhibit the production of trophic factors required for osteoblast lineage cell maintenance, ultimately leading to HSPC mobilization.
Details
- Title: Subtitle
- Expression of the G-CSF receptor in monocytic cells is sufficient to mediate hematopoietic progenitor mobilization by G-CSF in mice
- Creators
- Matthew J. Christopher - Washington University in St. LouisMahil Rao - Washington University in St. LouisFulu Liu - Washington University in St. LouisJill R. Woloszynek - Washington University in St. LouisDaniel C. Link - Washington University in St. Louis
- Resource Type
- Journal article
- Publication Details
- The Journal of experimental medicine, Vol.208(2), pp.251-260
- DOI
- 10.1084/jem.20101700
- PMID
- 21282380
- PMCID
- PMC3039862
- NLM abbreviation
- J Exp Med
- ISSN
- 0022-1007
- eISSN
- 1540-9538
- Publisher
- Rockefeller Univ Press
- Number of pages
- 10
- Grant note
- R01 HL60772 / National Institutes of Health; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA R01HL060772 / NATIONAL HEART, LUNG, AND BLOOD INSTITUTE; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Heart Lung & Blood Institute (NHLBI)
- Language
- English
- Date published
- 02/14/2011
- Academic Unit
- Critical Care; Stead Family Department of Pediatrics
- Record Identifier
- 9984775275202771
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