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Transcriptomic analyses of murine resolution-phase macrophages.

Stables, MJ; Shah, S; Camon, EB; Lovering, RC; Newson, J; Bystrom, J; ... Gilroy, DW; + view all (2011) Transcriptomic analyses of murine resolution-phase macrophages. Blood , 118 (26) e192 - e208. 10.1182/blood-2011-04-345330.

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Abstract

Macrophages are either classically (M1) or alternatively-activated (M2). Whereas this nomenclature was generated from monocyte-derived macrophages treated in vitro with defined cytokine stimuli, the phenotype of in vivo-derived macrophages is less understood. We completed Affymetrix-based transcriptomic analysis of macrophages from the resolution phase of a zymosan-induced peritonitis. Compared with macrophages from hyperinflamed mice possessing a pro-inflammatory nature as well as naive macrophages from the uninflamed peritoneum, resolution-phase macrophages (rM) are similar to monocyte-derived dendritic cells (DCs), being CD209a positive but lacking CD11c. They are enriched for antigen processing/presentation (MHC class II [H2-Eb1, H2-Ab1, H2-Ob, H2-Aa], CD74, CD86), secrete T- and B-lymphocyte chemokines (Xcl1, Ccl5, Cxcl13) as well as factors that enhance macrophage/DC development, and promote DC/T cell synapse formation (Clec2i, Tnfsf4, Clcf1). rM are also enriched for cell cycle/proliferation genes as well as Alox15, Timd4, and Tgfb2, key systems in the termination of leukocyte trafficking and clearance of inflammatory cells. Finally, comparison with in vitro-derived M1/M2 shows that rM are neither classically nor alternatively activated but possess aspects of both definitions consistent with an immune regulatory phenotype. We propose that macrophages in situ cannot be rigidly categorized as they can express many shades of the inflammatory spectrum determined by tissue, stimulus, and phase of inflammation.

Type:Article
Title:Transcriptomic analyses of murine resolution-phase macrophages.
Location:United States
DOI:10.1182/blood-2011-04-345330
Language:English
Keywords:Animals, Bone Marrow Cells, Cells, Cultured, Female, Flow Cytometry, Gene Expression Profiling, Macrophages, Male, Mice, Mice, Inbred C57BL, Oligonucleotide Array Sequence Analysis, Peritonitis, Reverse Transcriptase Polymerase Chain Reaction, Transcriptome, Zymosan
UCL classification:UCL > School of Life and Medical Sciences > Faculty of Life Sciences > Biosciences (Division of)
UCL > School of Life and Medical Sciences > Faculty of Medical Sciences > Medicine (Division of) > Metabolism and Experimental Therapeutics
UCL > School of Life and Medical Sciences > Faculty of Population Health Sciences > Institute of Cardiovascular Science

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