Transcriptional profiling of the human monocyte-to-macrophage differentiation and polarization: new molecules and patterns of gene expression.

Journal article

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.

Authors: Martinez, F; Gordon, S; Locati, M; Mantovani, A

• Publication status: Published
• Journal: Journal of Immunology
• Volume: 177
• Issue: 10
• Pages: 7303-7311
• Publication date: 2006-11-01
• DOI: 10.4049/jimmunol.177.10.7303
• EISSN: 1550-6606
• ISSN: 0022-1767
• Language: English
• Keywords: Interleukin-4; Lipid Metabolism; Cell Polarity; Macrophage Colony-Stimulating Factor; Receptors, G-Protein-Coupled; Transcription, Genetic; Macrophage Activation; Cells, Cultured; Gene Expression Profiling; Interferon-gamma; Cell Differentiation; Proteome; Macrophages; Humans; Monocytes; Chemokines