101. Specific Contributions of CSF-1 and GM-CSF to the Dynamics of the Mononuclear Phagocyte System.
- Author
-
Louis C, Cook AD, Lacey D, Fleetwood AJ, Vlahos R, Anderson GP, and Hamilton JA
- 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, Gene Expression Regulation, Granulocyte-Macrophage Colony-Stimulating Factor antagonists & inhibitors, Granulocyte-Macrophage Colony-Stimulating Factor genetics, Lipopolysaccharides, Macrophage Colony-Stimulating Factor antagonists & inhibitors, Macrophage Colony-Stimulating Factor genetics, Macrophages drug effects, Macrophages pathology, Mice, Monocytes drug effects, Monocytes pathology, Peritonitis chemically induced, Peritonitis genetics, Peritonitis pathology, Pneumonia chemically induced, Pneumonia genetics, 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, Granulocyte-Macrophage Colony-Stimulating Factor immunology, Macrophage Colony-Stimulating Factor immunology, Macrophages immunology, Monocytes immunology, Peritonitis immunology, Pneumonia immunology
- 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., (Copyright © 2015 by The American Association of Immunologists, Inc.)
- Published
- 2015
- Full Text
- View/download PDF