Sequential expression of macrophage anti-microbial/inflammatory and wound healing markers following innate, alternative and classical activation

Menzies, F M; Henriquez, F L; Alexander, J; Roberts, C W

doi:10.1111/j.1365-2249.2009.04086.x

Cited by 90Immune cells in cancerWound Healing and TreatmentsPhagocytosis and Immune Regulation

Sequential expression of macrophage anti-microbial/inflammatory and wound healing markers following innate, alternative and classical activation

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Menzies, F M, Henriquez, F L, Alexander, J, Roberts, C W·2010·Clinical and Experimental Immunology

DOI 10.1111/j.1365-2249.2009.04086.xPMC PMC2883107

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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.

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M2 microglial cells are characterized by thin cellular bodies and ramified processes.
“The M2 microglial cells are characterized by thin cellular bodies and ramified processes (Menzies et al., 2010; Komori et al., 2011; Varnum and Ikezu, 2012; Jones and Bouvier, 2014; Zhou et al., 2014).”
From The role of microglia in retinal neurodegeneration: Alzheimer’s disease, parkinson, and glaucoma. (2017) · cites this paper as Menzies et al., 2010
A comprehensive in vivo macrophage phenotype cannot be deduced solely from a limited set of phenotypic markers.
“Additionally, a comprehensive in vivo Mp phenotype cannot be deduced solely from a limited set of phenotypic markers, as different M2a-associated genes or proteins can exhibit entirely different temporal regulation and can be coexpressed with M1-associated markers [19,25,33,60,78].”
From Macrophage phenotypes during tissue repair (2013) · cites this paper as [25]

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Authors: Menzies, F. M., Henriquez, F. L., Alexander, J., & Roberts, C. W.
Affiliations: University of Strathclyde (GB)
University of the West of Scotland (GB)
Corresponding author: Roberts, C W
ORCID: Menzies, F M
Henriquez, F L
Roberts, C W
Venue: Clinical and Experimental Immunology
Publisher: Oxford University Press (OUP)
Published: 2010-01-05
Volume: 160
Issue: 3
Pages: 369-379
ISSN: 0009-9104 (ISSN-L)
1365-2249
DOI: 10.1111/j.1365-2249.2009.04086.x
PMC: PMC2883107
OpenAlex: W1556188925
Cited by: 90
References: 57
Citations by year: 2026: 1 · 2025: 3 · 2024: 2 · 2023: 3 · 2022: 4 · 2021: 7 · 2020: 3 · 2019: 5 · 2018: 5 · 2017: 7 · 2016: 9 · 2015: 9 · 2014: 8 · 2013: 9 · 2012: 8
FWCI: 3.29
Type: journal article
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Licence: academic.oup.com/journals/pages/open_access/funder_policies/chorus/standard_publication_model (vor)
Locations: Clinical & Experimental Immunology (publishedVersion)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
Strathprints: The University of Strathclyde institutional repository (University of Strathclyde) (submittedVersion)
Topics: Life Sciences › Immunology and Microbiology › Immunology › Immune cells in cancer
Health Sciences › Medicine › Rehabilitation › Wound Healing and Treatments
Life Sciences › Immunology and Microbiology › Immunology › Phagocytosis and Immune Regulation
Keywords: macrophage activation, macrophage polarization, alternative activation, classical activation, innate immunity, nitric oxide synthase 2, Dectin-1, Fizz1, Ym1, arginase, interferon-gamma, lipopolysaccharide, wound healing, macrophage plasticity
MeSH terms: Dectin-1, Animals, Antiviral Agents, Arginase, beta-N-Acetylhexosaminidases, Gene Expression Regulation, Immunity, Innate, Interferon-gamma, Macrophage Activation, Macrophages, Male, Membrane Proteins, Mice, Inbred BALB C, Nerve Tissue Proteins, Wound Healing, Biomarkers, Inflammation Mediators, Intercellular Signaling Peptides and Proteins, Lectins, Lectins, C-Type, Mice, Nitric Oxide Synthase Type II, Interleukin-12 Subunit p40

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Sequential expression of macrophage anti-microbial/inflammatory and wound healing markers following innate, alternative and classical activation

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