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

Cynthia Louis; Andrew D Cook; Derek Lacey; Andrew J Fleetwood; Ross Vlahos; Gary P Anderson; John A Hamilton

doi:10.4049/jimmunol.1500369

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

J Immunol. 2015 Jul 1;195(1):134-44. doi: 10.4049/jimmunol.1500369. Epub 2015 May 27.

Authors

Cynthia Louis¹, Andrew D Cook¹, Derek Lacey², Andrew J Fleetwood¹, Ross Vlahos³, Gary P Anderson⁴, John A Hamilton⁵

Affiliations

¹ Department of Medicine, The University of Melbourne, Royal Melbourne Hospital, Parkville, Victoria 3050, Australia;
² Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria 3052, Australia; Department of Medical Biology, The University of Melbourne, Melbourne, Victoria 3052, Australia;
³ Lung Health Research Centre, Department of Pharmacology and Therapeutics, The University of Melbourne, Parkville, Victoria 3010, Australia; School of Health Sciences, Royal Melbourne Institute of Technology University, Bundoora, Victoria 3083, Australia; and Health Innovations Research Institute, Royal Melbourne Institute of Technology University, Bundoora, Victoria 3083, Australia.
⁴ Lung Health Research Centre, Department of Pharmacology and Therapeutics, The University of Melbourne, Parkville, Victoria 3010, Australia;
⁵ Department of Medicine, The University of Melbourne, Royal Melbourne Hospital, Parkville, Victoria 3050, Australia; jahami@unimelb.edu.au.

PMID: 26019271
DOI: 10.4049/jimmunol.1500369

Abstract

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

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
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
fms-Like Tyrosine Kinase 3 / genetics
fms-Like Tyrosine Kinase 3 / immunology

Substances

Antibodies, Monoclonal
Antibodies, Neutralizing
Antigens, Ly
Ccr7 protein, mouse
Cytokines
Lipopolysaccharides
Ly-6C antigen, mouse
Receptors, CCR7
Thioglycolates
2-mercaptoacetate
Macrophage Colony-Stimulating Factor
Granulocyte-Macrophage Colony-Stimulating Factor
Flt3 protein, mouse
fms-Like Tyrosine Kinase 3