title: Specific Contributions of CSF-1 and GM-CSF to the Dynamics of the Mononuclear Phagocyte System.
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.
authors.affiliation: Department of Medicine, The University of Melbourne, Royal Melbourne Hospital, Parkville, Victoria 3050, Australia;
authors.forename: Cynthia
authors.initials: C
authors.lastname: Louis
authors.affiliation: Department of Medicine, The University of Melbourne, Royal Melbourne Hospital, Parkville, Victoria 3050, Australia;
authors.forename: Andrew D
authors.initials: AD
authors.lastname: Cook
authors.affiliation: Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria 3052, Australia; Department of Medical Biology, The University of Melbourne, Melbourne, Victoria 3052, Australia;
authors.forename: Derek
authors.initials: D
authors.lastname: Lacey
authors.affiliation: Department of Medicine, The University of Melbourne, Royal Melbourne Hospital, Parkville, Victoria 3050, Australia;
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Fleetwood
authors.affiliation: 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.
authors.forename: Ross
authors.initials: R
authors.lastname: Vlahos
authors.affiliation: Lung Health Research Centre, Department of Pharmacology and Therapeutics, The University of Melbourne, Parkville, Victoria 3010, Australia;
authors.forename: Gary P
authors.initials: GP
authors.lastname: Anderson
authors.affiliation: Department of Medicine, The University of Melbourne, Royal Melbourne Hospital, Parkville, Victoria 3050, Australia; jahami@unimelb.edu.au.
authors.forename: John A
authors.initials: JA
authors.lastname: Hamilton
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D057134:Antibodies, Neutralizing / Q000494:pharmacology; D000950:Antigens, Ly / Q000235:genetics / Q000276:immunology; D002452:Cell Count; D016207:Cytokines / Q000235:genetics / Q000276:immunology; D003713:Dendritic Cells / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D005786:Gene Expression Regulation; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000037:antagonists & inhibitors / Q000235:genetics / Q000276:immunology*; D008070:Lipopolysaccharides; D016173:Macrophage Colony-Stimulating Factor / Q000037:antagonists & inhibitors / Q000235:genetics / Q000276:immunology*; D008264:Macrophages / Q000187:drug effects / Q000276:immunology* / Q000473:pathology; D051379:Mice; D009000:Monocytes / Q000187:drug effects / Q000276:immunology* / Q000473:pathology; D010538:Peritonitis / Q000139:chemically induced / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D011014:Pneumonia / Q000139:chemically induced / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D061251:Primary Cell Culture; D054400:Receptors, CCR7 / Q000235:genetics / Q000276:immunology; D015398:Signal Transduction; D013864:Thioglycolates; D051941:fms-Like Tyrosine Kinase 3 / Q000235:genetics / Q000276:immunology
chemical_list: D000911:Antibodies, Monoclonal; D057134:Antibodies, Neutralizing; D000950:Antigens, Ly; C515371:Ccr7 protein, mouse; D016207:Cytokines; D008070:Lipopolysaccharides; C494192:Ly-6C antigen, mouse; D054400:Receptors, CCR7; D013864:Thioglycolates; C017487:2-mercaptoacetate; D016173:Macrophage Colony-Stimulating Factor; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; C497971:Flt3 protein, mouse; D051941:fms-Like Tyrosine Kinase 3