title: 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.
authors.affiliation: Department of Medicine, Arthritis and Inflammation Research Centre, University of Melbourne, The Royal Melbourne Hospital, Parkville, Victoria 3050, Australia.
authors.forename: Derek C
authors.initials: DC
authors.lastname: Lacey
authors.forename: Adrian
authors.initials: A
authors.lastname: Achuthan
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Fleetwood
authors.forename: Hang
authors.initials: H
authors.lastname: Dinh
authors.forename: John
authors.initials: J
authors.lastname: Roiniotis
authors.forename: Glen M
authors.initials: GM
authors.lastname: Scholz
authors.forename: Melody W
authors.initials: MW
authors.lastname: Chang
authors.forename: Sandra K
authors.initials: SK
authors.lastname: Beckman
authors.forename: Andrew D
authors.initials: AD
authors.lastname: Cook
authors.forename: John A
authors.initials: JA
authors.lastname: Hamilton
mesh_terms: D000818:Animals; D019070:Cell Lineage / Q000235:genetics / Q000276:immunology; D002478:Cells, Cultured; D005260:Female; D005786:Gene Expression Regulation / Q000276:immunology; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000502:physiology*; D006801:Humans; D016130:Immunophenotyping; D016173:Macrophage Colony-Stimulating Factor / Q000276:immunology*; D008264:Macrophages / Q000166:cytology* / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009000:Monocytes / Q000166:cytology / Q000276:immunology
chemical_list: D016173:Macrophage Colony-Stimulating Factor; D016178:Granulocyte-Macrophage Colony-Stimulating Factor