Polarization profiles of human M-CSF-generated macrophages and comparison of M1-markers in classically activated macrophages from GM-CSF and M-CSF origin
Polarization profiles of human M-CSF-generated macrophages and comparison of M1-markers in classically activated macrophages from GM-CSF and M-CSF origin
复制标题
DOI：
10.1016/j.cellimm.2013.01.010
复制
发表时间：
2013-01-01
影响因子：
4.3
通讯作者：
Lecureur, Valerie
中科院分区：
文献类型：
--
作者：
Jaguin, Marie;Houlbert, Noemie;Lecureur, Valerie
单核细胞/巨噬细胞（M Phi），被认为是可塑性细胞，可以根据其微环境分化成促炎（M1）亚型，也称为经典活化亚型，或抗炎替代活化亚型（M2）。小鼠极化M Phi的表型标记物已被广泛研究，而它们的人类对应物仍然较少表征。因此，本研究的主要目的是仔细表征由M-CSF处理的血液单核细胞产生的原代人M Phi的表型和基因组标志物，并在脂多糖和干扰素-γ（对于M1）或白细胞介素（1 L）-4（对于M2）的作用下极化为M1或M2亚型。膜表达的标志物CD 80和CD 200 R被认为是特定的人M1和M2极化M φ，分别，而相比之下，甘露糖受体（CD 206）的表达没有区分M1和M2。mRNA表达分析进一步鉴定了M1极化的六个标志物（IL-12 p35、CXCL 10、CXCL 11、CCL 5、CCR 7和IDO 1）、M2极化的五个标志物（TGF-β、CCL 14、CCL 22、SR-B1和PPAR γ）和参与MPhi极化的转录因子。人M-CSF产生的M Phi向M1或M2亚型转化的能力也与TNF α、IL-1 β、IL-12 p40、CXCL 10和IL-10（对于M1）或CCL 22（对于M2）的分泌增强相关。此外，M1标记物在M-CSF-和GM-CSF-M Phi中的表达的比较显示了相似性，所述M-CSF-和GM-CSF-M Phi朝向M1亚型极化。总之，我们证明了人M-CSF M Phi在IFN γ/LPS刺激后可以向M1型转化。此外，在本研究中鉴定的人类极化MO的M1和M2标志物可能有助于更好地鉴定人类M Phi亚型，特别是在组织水平，以便更好地理解它们各自在病理发展中的作用。(c)2013 Elsevier Inc. All rights reserved.
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.