Defining GM-CSF– and Macrophage-CSF–Dependent Macrophage Responses by In Vitro Models
- 1 June 2012
- journal article
- research article
- Published by The American Association of Immunologists in The Journal of Immunology
- Vol. 188 (11), 5752-5765
- https://doi.org/10.4049/jimmunol.1103426
Abstract
GM-CSF and M-CSF (CSF-1) induce different phenotypic changes in macrophage lineage populations. The nature, extent, and generality of these differences were assessed by comparing the responses to these CSFs, either alone or in combination, in various human and murine macrophage lineage populations. The differences between the respective global gene expression profiles of macrophages, derived from human monocytes by GM-CSF or M-CSF, were compared with the differences between the respective profiles for macrophages, derived from murine bone marrow cells by each CSF. Only 17% of genes regulated differently by these CSFs were common across the species. Whether a particular change in relative gene expression is by direct action of a CSF can be confounded by endogenous mediators, such as type I IFN, IL-10, and activin A. Time-dependent differences in cytokine gene expression were noted in human monocytes treated with the CSFs; in this system, GM-CSF induced a more dramatic expression of IFN-regulated factor 4 (IRF4) than of IRF5, whereas M-CSF induced IRF5 but not IRF4. In the presence of both CSFs, some evidence of "competition" at the level of gene expression was observed. Care needs to be exercised when drawing definitive conclusions from a particular in vitro system about the roles of GM-CSF and M-CSF in macrophage lineage biology.Keywords
This publication has 51 references indexed in Scilit:
- Activin A skews macrophage polarization by promoting a proinflammatory phenotype and inhibiting the acquisition of anti-inflammatory macrophage markersBlood, 2011
- Meta-analysis of lineage-specific gene expression signatures in mouse leukocyte populationsImmunobiology, 2010
- Trophic macrophages in development and diseaseNature Reviews Immunology, 2009
- The generation and properties of human macrophage populations from hemopoietic stem cellsJournal of Leukocyte Biology, 2009
- Exploring the full spectrum of macrophage activationNature Reviews Immunology, 2008
- Colony-stimulating factors in inflammation and autoimmunityNature Reviews Immunology, 2008
- Novel insights into the relationships between dendritic cell subsets in human and mouse revealed by genome-wide expression profilingGenome Biology, 2008
- Intrasplenic steady-state dendritic cell precursors that are distinct from monocytesNature Immunology, 2006
- Macrophage Polarization Comes of AgeImmunity, 2005
- Generation of large numbers of dendritic cells from mouse bone marrow cultures supplemented with granulocyte/macrophage colony-stimulating factor.The Journal of Experimental Medicine, 1992