Specific Contributions of CSF-1 and GM-CSF to the Dynamics of the Mononuclear Phagocyte System

M-CSF (or CSF-1) and GM-CSF can regulate the development and function of the mononuclear phagocyte system (MPS). To address some of the outstanding and sometimes conflicting issues surrounding this biology, we undertook a comparative analysis of the effects of neutralizing mAbs to these CSFs on muri...

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Bibliographic Details
Published in:The Journal of immunology (1950) 2015-07, Vol.195 (1), p.134-144
Main Authors: Louis, Cynthia, Cook, Andrew D, Lacey, Derek, Fleetwood, Andrew J, Vlahos, Ross, Anderson, Gary P, Hamilton, John A
Format: Article
Language:English
Subjects:
Animals
Antibodies, Monoclonal - pharmacology
Antibodies, Neutralizing - pharmacology
Antigens, Ly - genetics
Antigens, Ly - immunology
Cell Count
Cytokines - genetics
Cytokines - immunology
Dendritic Cells - drug effects
Dendritic Cells - immunology
Dendritic Cells - pathology
fms-Like Tyrosine Kinase 3 - genetics
fms-Like Tyrosine Kinase 3 - immunology
Gene Expression Regulation
Granulocyte-Macrophage Colony-Stimulating Factor - antagonists & inhibitors
Granulocyte-Macrophage Colony-Stimulating Factor - genetics
Granulocyte-Macrophage Colony-Stimulating Factor - immunology
Lipopolysaccharides
Macrophage Colony-Stimulating Factor - antagonists & inhibitors
Macrophage Colony-Stimulating Factor - genetics
Macrophage Colony-Stimulating Factor - immunology
Macrophages - drug effects
Macrophages - immunology
Macrophages - pathology
Mice
Monocytes - drug effects
Monocytes - immunology
Monocytes - pathology
Peritonitis - chemically induced
Peritonitis - genetics
Peritonitis - immunology
Peritonitis - pathology
Pneumonia - chemically induced
Pneumonia - genetics
Pneumonia - immunology
Pneumonia - pathology
Primary Cell Culture
Receptors, CCR7 - genetics
Receptors, CCR7 - immunology
Signal Transduction
Thioglycolates
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Summary:M-CSF (or CSF-1) and GM-CSF can regulate the development and function of the mononuclear phagocyte system (MPS). To address some of the outstanding and sometimes conflicting issues surrounding this biology, we undertook a comparative analysis of the effects of neutralizing mAbs to these CSFs on murine MPS populations in the steady-state and during acute inflammatory reactions. CSF-1 neutralization, but not of GM-CSF, in normal mice rapidly reduced the numbers of more mature Ly6C(-) monocytes in blood and bone marrow, without any effect on proliferating precursors, and also the numbers of the resident peritoneal macrophages, observations consistent with CSF-1 signaling being essential only at a relatively late state in steady-state MPS development; in contrast, GM-CSF neutralization had no effect on the numbers of these particular populations. In Ag-induced peritonitis (AIP), thioglycolate-induced peritonitis, and LPS-induced lung inflammation, CSF-1 neutralization lowered inflammatory macrophage number; in the AIP model, this reduced number was not due to suppressed proliferation. More detailed studies with the convenient AIP model indicated that CSF-1 neutralization led to a relatively uniform reduction in all inflammatory cell populations; GM-CSF neutralization, in contrast, was more selective, resulting in the preferential loss among the MPS populations of a cycling, monocyte-derived inflammatory dendritic cell population. Some mechanistic options for the specific CSF-dependent biologies enumerated are discussed.
ISSN:0022-1767
1550-6606
DOI:10.4049/jimmunol.1500369