title: Novel macrophage polarization model: from gene expression to identification of new anti-inflammatory molecules.
abstract: Plasticity is a well-known property of macrophages that is controlled by different changes in environmental signals. Macrophage polarization is regarded as a spectrum of activation phenotypes adjusted from one activation extreme, the classic (M1), to the other, the alternative (M2) activation. Here we show, in vitro and in vivo, that both M1 and M2 macrophage phenotypes are tightly coupled to specific patterns of gene expression. Novel M2-associated markers were characterized and identified as genes controlling the extracellular metabolism of ATP to generate pyrophosphates (PPi). Stimulation of M1 macrophages with PPi dampens both NLR and TLR signaling and thus mediates cytokine production. In this context extracellular PPi enhanced the resolution phase of a murine peritonitis model via a decrease in pro-inflammatory cytokine production. Therefore, our study reveals an additional level of plasticity modulating the resolution of inflammation.
authors.affiliation: Faculty of Life Science, University of Manchester, Michael Smith Building D3315, Manchester, M13 9PT, UK.
authors.forename: Gloria
authors.initials: G
authors.lastname: Lopez-Castejón
authors.forename: Alberto
authors.initials: A
authors.lastname: Baroja-Mazo
authors.forename: Pablo
authors.initials: P
authors.lastname: Pelegrín
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism*; D000818:Animals; D015153:Blotting, Western; D016207:Cytokines / Q000378:metabolism; D011756:Diphosphates / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D005786:Gene Expression Regulation / Q000502:physiology*; D008262:Macrophage Activation / Q000502:physiology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008954:Models, Biological; D010538:Peritonitis / Q000139:chemically induced / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D051193:Toll-Like Receptors / Q000378:metabolism; D015054:Zymosan / Q000633:toxicity
chemical_list: D016207:Cytokines; D011756:Diphosphates; D051193:Toll-Like Receptors; D000255:Adenosine Triphosphate; D015054:Zymosan