Journal
CELLULAR IMMUNOLOGY
Volume 281, Issue 1, Pages 51-61Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.cellimm.2013.01.010
Keywords
Macrophage; Polarization; Markers; Cytokine/chemokine; Transcription factors; M-CSF
Categories
Funding
- Fondation Coeur et Arteres [FCA 09T3]
- French Ministry of Research
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Monocytes/macrophages (M Phi), considered as plastic cells, can differentiate into either a pro-inflammatory (M1) subtype, also known as a classically activated subtype, or an anti-inflammatory alternatively activated subtype (M2) according to their microenvironment. Phenotypic markers of mouse polarized M Phi have been extensively studied, whereas their human counterparts remain less characterized. The main goal of this study was therefore to carefully characterize phenotypic and genomic markers of primary human M Phi generated from M-CSF-treated blood monocytes and polarized towards M1 or M2 subtype upon the action of lipopolysaccharide and interferon-gamma (for M1) or interleukin (1L)-4 (for M2). Membrane expression of the markers CD80 and CD200R was found to be specific of human M1 and M2 polarized M Phi, respectively, whereas, by contrast, mannose receptor (CD206) expression did not discriminate between M1 and M2. mRNA expression analysis further identified six markers of M1 polarization (IL-12p35, CXCL10, CXCL11, CCL5, CCR7 and 1DO1), five markers of M2 polarization (TGF-beta, CCL14, CCL22, SR-B1 and PPAR gamma) and transcription factors involved in M Phi polarization. Ability of human M-CSF-generated M Phi to polarize toward M1 or M2 subtype was also associated with enhanced secretion of TNF alpha, IL-1 beta, IL-12p40, CXCL10 and IL-10 (for M1) or CCL22 (for M2). Moreover, the comparison of the expression of M1 markers in M-CSF- and GM-CSF-M Phi polarized towards M1 subtype has revealed similarities. In conclusion, we demonstrated that human M-CSF M Phi can polarize toward a M1 type after IFN gamma/LPS stimulation. Moreover, the M1 and M2 markers of human polarized MO identified in the present study may be useful to better identify human M Phi subtypes, particularly at the tissue level, in order to better understand their respective roles in the development of pathologies. (c) 2013 Elsevier Inc. All rights reserved.
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