An antibody against the colony-stimulating factor 1 receptor (CSF1R) depletes the resident subset of monocytes and tissue and tumor-associated macrophages but does not inhibit inflammation

MacDonald, Kelli P.A, Palmer, James S., Cronau, Stephen, Seppanen, Elke Jane, Olver, Stuart, Raffelt, Neil C., Kuns, Rachel, Pettit, Allison R., Clouston, Andrew, Wainwright, Brandon J., Branstetter, Dan, Smith, Jeffrey, Paxton, Raymond J., Cerretti, Douglas Pat, Bonham, Lynn, Hill, Geoffrey R. and Hume, David (2010) An antibody against the colony-stimulating factor 1 receptor (CSF1R) depletes the resident subset of monocytes and tissue and tumor-associated macrophages but does not inhibit inflammation. Blood, 116 19: 3955-3963. doi:10.1182/blood-2010-02-266296


Author MacDonald, Kelli P.A
Palmer, James S.
Cronau, Stephen
Seppanen, Elke Jane
Olver, Stuart
Raffelt, Neil C.
Kuns, Rachel
Pettit, Allison R.
Clouston, Andrew
Wainwright, Brandon J.
Branstetter, Dan
Smith, Jeffrey
Paxton, Raymond J.
Cerretti, Douglas Pat
Bonham, Lynn
Hill, Geoffrey R.
Hume, David
Title An antibody against the colony-stimulating factor 1 receptor (CSF1R) depletes the resident subset of monocytes and tissue and tumor-associated macrophages but does not inhibit inflammation
Journal name Blood   Check publisher's open access policy
ISSN 0006-4971
1528-0020
Publication date 2010-11-11
Year available 2010
Sub-type Article (original research)
DOI 10.1182/blood-2010-02-266296
Open Access Status
Volume 116
Issue 19
Start page 3955
End page 3963
Total pages 9
Place of publication Washington, DC, U.S.A.
Publisher American Society of Hematology
Collection year 2011
Language eng
Formatted abstract
The development of the mononuclear phagocyte system requires macrophage colony-stimulating factor (CSF-1) signaling through the CSF-1 receptor (CSF1R, CD115). We examined the effect of an antibody against CSF1R on macrophage homeostasis and function using the MacGreen transgenic mouse (csf1r-enhanced green fluorescent protein) as a reporter. The administration of a novel CSF1R blocking antibody selectively reduced the CD115+Gr-1neg monocyte precursor of resident tissue macrophages. CD115+Gr-1 + inflammatory monocytes were correspondingly increased, supporting the view that monocytes are a developmental series. Within tissue, the antibody almost completely depleted resident macrophage populations in the peritoneum, gastrointestinal tract, liver, kidney, and skin, but not in the lung or female reproductive organs. CSF1R blockade reduced the numbers of tumor-associated macrophages in syngeneic tumor models, suggesting that these cells are resident type macrophages. Conversely, it had no effect on inflammatory monocyte recruitment in models, including lipopolysaccharide-induced lung inflammation, wound healing, peritonitis, and severe acute graft-versus-host disease. Depletion of resident tissue macrophages from bone marrow transplantation recipients actually resulted in accelerated pathology and exaggerated donor T-cell activation. The data indicate that CSF1R signaling is required only for the maturation and replacement of resident-type monocytes and tissue macrophages, and is not required for monocyte production or inflammatory function. © 2010 by The American Society of Hematology.
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ
Additional Notes Prepublished online as a Blood First Edition Paper on 3 August, 2010.

Document type: Journal Article
Sub-type: Article (original research)
Collections: UQ Centre for Clinical Research Publications
Official 2011 Collection
Institute for Molecular Bioscience - Publications
 
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Created: Mon, 31 Jan 2011, 13:20:02 EST by Susan Allen on behalf of Institute for Molecular Bioscience