title: Sequential expression of macrophage anti-microbial/inflammatory and wound healing markers following innate, alternative and classical activation.
abstract: The present study examines the temporal dynamics of macrophage activation marker expression in response to variations in stimulation. We demonstrate that markers can be categorized as 'early' (expressed most abundantly at 6 h post-stimulation) or 'late' (expressed at 24 h post-stimulation). Thus nos2 and p40 (IL-12/IL-23) are early markers of innate and classical activation, while dectin-1 and mrc-1 are early markers and fizz1 (found in inflammatory zone-1) and ym1 are late markers of alternative activation. Furthermore, argI is a late marker of both innate and alternative activation. The ability of interferon (IFN)-gamma to alter these activation markers was studied at both the protein level and gene level. As reported previously, IFN-gamma was able to drive macrophages towards the classical phenotype by enhancing nos2 gene expression and enzyme activity and p40 (IL-12/IL-23) gene expression in lipopolysaccharide (LPS)-stimulated macrophages. IFN-gamma antagonized alternative macrophage activation, as evident by reduced expression of dectin-1, mrc-1, fizz1 and ym1 mRNA transcripts. In addition, IFN-gamma antagonized arginase activity irrespective of whether macrophages were activated innately or alternatively. Our data explain some apparent contradictions in the literature, demonstrate temporal plasticity in macrophage activation states and define for the first time 'early' and 'late' markers associated with anti-microbial/inflammatory and wound healing responses, respectively.
authors.affiliation: Strathclyde Institute for Pharmacy and Biomedical Sciences, University of Strathclyde, Glasgow, UK.
authors.forename: F M
authors.initials: FM
authors.lastname: Menzies
authors.forename: F L
authors.initials: FL
authors.lastname: Henriquez
authors.forename: J
authors.initials: J
authors.lastname: Alexander
authors.forename: C W
authors.initials: CW
authors.lastname: Roberts
mesh_terms: D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology; D001119:Arginase / Q000096:biosynthesis / Q000276:immunology; D015415:Biomarkers / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects / Q000276:immunology*; D007113:Immunity, Innate / Q000187:drug effects / Q000276:immunology; D018836:Inflammation Mediators / Q000276:immunology* / Q000378:metabolism; D036341:Intercellular Signaling Peptides and Proteins / Q000096:biosynthesis / Q000276:immunology; D007371:Interferon-gamma / Q000494:pharmacology; D053762:Interleukin-12 Subunit p40 / Q000096:biosynthesis / Q000276:immunology; D037102:Lectins / Q000096:biosynthesis / Q000276:immunology; D037181:Lectins, C-Type; D008262:Macrophage Activation / Q000187:drug effects / Q000276:immunology*; D008264:Macrophages / Q000276:immunology* / Q000378:metabolism; D008297:Male; D008565:Membrane Proteins / Q000096:biosynthesis / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D009419:Nerve Tissue Proteins / Q000096:biosynthesis / Q000276:immunology; D052247:Nitric Oxide Synthase Type II / Q000096:biosynthesis / Q000276:immunology; D014945:Wound Healing / Q000187:drug effects / Q000276:immunology*; D001619:beta-N-Acetylhexosaminidases / Q000096:biosynthesis / Q000276:immunology; D000099181:Dectin-1
chemical_list: D000998:Antiviral Agents; D001119:Arginase; D015415:Biomarkers; D018836:Inflammation Mediators; D036341:Intercellular Signaling Peptides and Proteins; D007371:Interferon-gamma; D053762:Interleukin-12 Subunit p40; D037102:Lectins; D037181:Lectins, C-Type; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D052247:Nitric Oxide Synthase Type II; D001619:beta-N-Acetylhexosaminidases; D000099181:Dectin-1; C413576:Retnla protein, mouse; C496317:Nos2 protein, mouse; C429541:Chil3 protein, mouse; C544448:Arg1 protein, mouse