Defining GM-CSF– and Macrophage-CSF–Dependent Macrophage Responses by In Vitro Models

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.

MICA/B expression in macrophage foam cells infiltrating atherosclerotic plaques

“…However, growth factors such as M-CSF and granulocyte/macrophage CSF (GM-CSF) induce distinct phenotypic changes in macrophage populations (Lacey et al, 2012). Recent work indicated that M-CSF increases SR-A expression in primary macrophages via p38 MAP kinase activation (Nikolic et al, 2011).…”

“…We confirmed that SR-A expression was frequently detected in AcLDL-loaded MDMs generated by our new method (Figure 2D We showed that MDMs can be induced by coculture with autologous non-adherent PBMCs without adding any growth factors (Figure 2). Recently, controversial issues have been raised concerning the nature of macrophages induced in vitro by growth factors such as M-CSF and GM-CSF (Fleetwood et al, 2007;Lacey et al, 2012). Also, recent work indicates that treatment with M-CSF up-regulates SR-A expression in macrophages (Nikolic et al, 2011).…”

Urokinase Plasminogen Activator Is a Central Regulator of Macrophage Three-Dimensional Invasion, Matrix Degradation, and Adhesion

“…Mouse bone marrow-derived macrophages (BMM) and human monocytederived macrophages (MDM) were prepared as before (50). Briefly, bone marrow cells from the femurs of mice were cultured in RPMI 1640 medium supplemented with 10% FCS, 2 mM GlutaMax-1, 100 U/ml penicillin, and 100 mg/ml streptomycin in the presence of M-CSF (CSF-1; 2000 U/ml).…”

“…On day 7, adherent cells were harvested. Human monocytes were purified from buffy coats (Red Cross Blood Bank, Melbourne, VIC, Australia) and MDM generated as before from M-CSF-treated cultures (50). Peritoneal exudate cells were elicited by i.p.…”

The ecto-ATPDase CD39 is involved in the acquisition of the immunoregulatory phenotype by M-CSF-macrophages and ovarian cancer tumor-associated macrophages: Regulatory role of IL-27

“…They also promote angiogenesis, tissue remodeling and wound healing. 2,3 Macrophages are plastic cells. Their phenotype and functions can be modulated, depending on their microenvironment.…”