Specific contributions of CSF-1 and GM-CSF to the dynamics of the mononuclear phagocyte system

Louis, C; Cook, AD; Lacey, D; Fleetwood, AJ; Vlahos, R; Anderson, GP; Hamilton, JA

Author(s): Louis, C; Cook, AD; Lacey, D; Fleetwood, AJ; Vlahos, R; Anderson, GP; Hamilton, JA;
Details: Publication Year 2015-07-01,Volume 195,Issue #1,Page 134-44
Journal Title: Journal of Immunology
Publication Type: Journal Article
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.
Publisher: ASI
Research Division(s): Molecular Genetics Of Cancer
PubMed ID: 26019271
Publisher's Version: https://doi.org/10.4049/jimmunol.1500369
Terms of Use/Rights Notice: Refer to copyright notice on published article.

Creation Date: 2015-06-15 09:53:28

Last Modified: 2015-07-14 03:00:22