Document Detail


Sequential expression of macrophage anti-microbial/inflammatory and wound healing markers following innate, alternative and classical activation.
MedLine Citation:
PMID:  20059482     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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:
F M Menzies; F L Henriquez; J Alexander; C W Roberts
Publication Detail:
Type:  Journal Article     Date:  2010-01-05
Journal Detail:
Title:  Clinical and experimental immunology     Volume:  160     ISSN:  1365-2249     ISO Abbreviation:  Clin. Exp. Immunol.     Publication Date:  2010 Jun 
Date Detail:
Created Date:  2010-06-18     Completed Date:  2010-07-09     Revised Date:  2011-07-28    
Medline Journal Info:
Nlm Unique ID:  0057202     Medline TA:  Clin Exp Immunol     Country:  England    
Other Details:
Languages:  eng     Pagination:  369-79     Citation Subset:  IM    
Affiliation:
Strathclyde Institute for Pharmacy and Biomedical Sciences, University of Strathclyde, Glasgow, UK.
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MeSH Terms
Descriptor/Qualifier:
Animals
Antiviral Agents / pharmacology
Arginase / biosynthesis,  immunology
Biological Markers / metabolism
Gene Expression Regulation / drug effects,  immunology*
Immunity, Innate / drug effects,  immunology
Inflammation Mediators / immunology*,  metabolism
Intercellular Signaling Peptides and Proteins / biosynthesis,  immunology
Interferon-gamma / pharmacology
Interleukin-12 Subunit p40 / biosynthesis,  immunology
Lectins / biosynthesis,  immunology
Macrophage Activation / drug effects,  immunology*
Macrophages / immunology*,  metabolism
Male
Membrane Proteins / biosynthesis,  immunology
Mice
Mice, Inbred BALB C
Nerve Tissue Proteins / biosynthesis,  immunology
Nitric Oxide Synthase Type II / biosynthesis,  immunology
Wound Healing / drug effects,  immunology*
beta-N-Acetylhexosaminidases / biosynthesis,  immunology
Chemical
Reg. No./Substance:
0/Antiviral Agents; 0/Biological Markers; 0/Inflammation Mediators; 0/Intercellular Signaling Peptides and Proteins; 0/Interleukin-12 Subunit p40; 0/Lectins; 0/Membrane Proteins; 0/Nerve Tissue Proteins; 0/Retnla protein, mouse; 0/dectin 1; 82115-62-6/Interferon-gamma; EC 1.14.13.39/Nitric Oxide Synthase Type II; EC 1.14.13.39/Nos2 protein, mouse; EC 3.2.1.52/Chi3l3 protein, mouse; EC 3.2.1.52/beta-N-Acetylhexosaminidases; EC 3.5.3.1/Arg1 protein, mouse; EC 3.5.3.1/Arginase
Comments/Corrections

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