Transcriptional profiling of the human monocyte-to-macrophage differentiation and polarization: new molecules and patterns of gene expression.
Comprehensive analysis of the gene expression profiles associated with human monocyte-to-macrophage differentiation and polarization toward M1 or M2 phenotypes led to the following main results: 1) M-CSF-driven monocyte-to-macrophage differentiation is associated with activation of cell cycle genes, substantiating the underestimated proliferation potential of monocytes. 2) M-CSF leads to expression of a substantial part of the M2 transcriptome, suggesting that under homeostatic conditions a default shift toward M2 occurs. 3) Modulation of genes involved in metabolic activities is a prominent feature of macrophage differentiation and polarization. 4) Lipid metabolism is a main category of modulated transcripts, with expected up-regulation of cyclo-oxygenase 2 in M1 cells and unexpected cyclo-oxygenase 1 up-regulation in M2 cells. 5) Each step is characterized by a different repertoire of G protein-coupled receptors, with five nucleotide receptors as novel M2-associated genes. 6) The chemokinome of polarized macrophages is profoundly diverse and new differentially expressed chemokines are reported. Thus, transcriptome profiling reveals novel molecules and signatures associated with human monocyte-to-macrophage differentiation and polarized activation which may represent candidate targets in pathophysiology.
Martinez
Fernando O
FO
Istituto Clinico Humanitas, Rozzano, Italy.
Gordon
Siamon
S
Locati
Massimo
M
Mantovani
Alberto
A
D002454:Cell Differentiation / Q000235:genetics* / Q000276:immunology*; D016764:Cell Polarity / Q000235:genetics* / Q000276:immunology*; D002478:Cells, Cultured; D018925:Chemokines / Q000096:biosynthesis / Q000235:genetics; D020869:Gene Expression Profiling; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology; D015847:Interleukin-4 / Q000494:pharmacology; D050356:Lipid Metabolism / Q000235:genetics / Q000276:immunology; D008262:Macrophage Activation / Q000235:genetics / Q000276:immunology; D016173:Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D008264:Macrophages / Q000145:classification / Q000166:cytology / Q000378:metabolism*; D009000:Monocytes / Q000166:cytology / Q000378:metabolism*; D020543:Proteome / Q000235:genetics / Q000276:immunology; D043562:Receptors, G-Protein-Coupled / Q000096:biosynthesis / Q000235:genetics; D014158:Transcription, Genetic
D018925:Chemokines; D020543:Proteome; D043562:Receptors, G-Protein-Coupled; D015847:Interleukin-4; D016173:Macrophage Colony-Stimulating Factor; D007371:Interferon-gamma