Full Text:   <1210>

Summary:  <281>

Suppl. Mater.: 

CLC number: 

On-line Access: 2022-05-13

Received: 2021-11-12

Revision Accepted: 2022-02-04

Crosschecked: 2022-05-13

Cited: 0

Clicked: 1228

Citations:  Bibtex RefMan EndNote GB/T7714


Shisheng SUN


-   Go to

Article info.
Open peer comments

Journal of Zhejiang University SCIENCE B 2022 Vol.23 No.5 P.407-422


Proteomic characterization of four subtypes of M2 macrophages derived from human THP-1 cells

Author(s):  Pengfei LI, Chen MA, Jing LI, Shanshan YOU, Liuyi DANG, Jingyu WU, Zhifang HAO, Jun LI, Yuan ZHI, Lin CHEN, Shisheng SUN

Affiliation(s):  College of Life Science, Northwest University, Xian 710069, China

Corresponding email(s):   suns@nwu.edu.cn

Key Words:  Macrophage, THP-1 cells, M2 subtype, Proteomics, Biological function

Pengfei LI, Chen MA, Jing LI, Shanshan YOU, Liuyi DANG, Jingyu WU, Zhifang HAO, Jun LI, Yuan ZHI, Lin CHEN, Shisheng SUN. Proteomic characterization of four subtypes of M2 macrophages derived from human THP-1 cells[J]. Journal of Zhejiang University Science B, 2022, 23(5): 407-422.

@article{title="Proteomic characterization of four subtypes of M2 macrophages derived from human THP-1 cells",
author="Pengfei LI, Chen MA, Jing LI, Shanshan YOU, Liuyi DANG, Jingyu WU, Zhifang HAO, Jun LI, Yuan ZHI, Lin CHEN, Shisheng SUN",
journal="Journal of Zhejiang University Science B",
publisher="Zhejiang University Press & Springer",

%0 Journal Article
%T Proteomic characterization of four subtypes of M2 macrophages derived from human THP-1 cells
%A Pengfei LI
%A Chen MA
%A Jing LI
%A Shanshan YOU
%A Liuyi DANG
%A Jingyu WU
%A Zhifang HAO
%A Jun LI
%A Yuan ZHI
%A Shisheng SUN
%J Journal of Zhejiang University SCIENCE B
%V 23
%N 5
%P 407-422
%@ 1673-1581
%D 2022
%I Zhejiang University Press & Springer
%DOI 10.1631/jzus.B2100930

T1 - Proteomic characterization of four subtypes of M2 macrophages derived from human THP-1 cells
A1 - Pengfei LI
A1 - Chen MA
A1 - Jing LI
A1 - Shanshan YOU
A1 - Liuyi DANG
A1 - Jingyu WU
A1 - Zhifang HAO
A1 - Jun LI
A1 - Yuan ZHI
A1 - Lin CHEN
A1 - Shisheng SUN
J0 - Journal of Zhejiang University Science B
VL - 23
IS - 5
SP - 407
EP - 422
%@ 1673-1581
Y1 - 2022
PB - Zhejiang University Press & Springer
ER -
DOI - 10.1631/jzus.B2100930

macrophages are widely distributed immune cells that contribute to tissue homeostasis. Human THP-1 cells have been widely used in various macrophage-associated studies, especially those involving pro-inflammatory M1 and anti-inflammatory M2 phenotypes. However, the molecular characterization of four m2 subtypes (M2a, M2b, M2c, and M2d) derived from THP-1 has not been fully investigated. In this study, we systematically analyzed the protein expression profiles of human THP-1-derived macrophages (M0, M1, M2a, M2b, M2c, and M2d) using quantitative proteomics approaches. The commonly and specially regulated proteins of the four m2 subtypes and their potential biological functions were further investigated. The results showed that M2a and M2b, and M2c and M2d have very similar protein expression profiles. These data could serve as an important resource for studies of macrophages using THP-1 cells, and provide a reference to distinguish different m2 subtypes in macrophage-associated diseases for subsequent clinical research.




Darkslateblue:Affiliate; Royal Blue:Author; Turquoise:Article


[1]Avila-Ponce de LeónU, Vazquez-JimenezA, Matadamas-GuzmanM, et al., 2021. Transcriptional and microenvironmental landscape of macrophage transition in cancer: a boolean analysis. Front Immunol, 12:642842.

[2]BaderGD, HogueCWV, 2003. An automated method for finding molecular complexes in large protein interaction networks. BMC Bioinformatics, 4:2.

[3]BatchuS, 2020. Progressive multiple sclerosis transcriptome deconvolution indicates increased M2 macrophages in inactive lesions. Eur Neurol, 83(4):433-435.

[4]BaumeierC, EscherF, AleshchevaG, et al., 2021. Plasminogen activator inhibitor-1 reduces cardiac fibrosis and promotes M2 macrophage polarization in inflammatory cardiomyopathy. Basic Res Cardiol, 116:1.

[5]Ben-Ari FuchsS, LiederI, StelzerG, et al., 2016. GeneAnalytics: an integrative gene set analysis tool for next generation sequencing, RNAseq and microarray data. OMICS, 20(3):139-151.

[6]BindeaG, MlecnikB, HacklH, et al., 2009. ClueGO: a Cytoscape plug-in to decipher functionally grouped gene ontology and pathway annotation networks. Bioinformatics, 25(8):1091-1093.

[7]BuschS, TalaminiM, BrennerS, et al., 2019. Circulating monocytes and tumor-associated macrophages express recombined immunoglobulins in glioblastoma patients. Clin Transl Med, 8(1):e18.

[8]ChanputW, MesJJ, WichersHJ, 2014. THP-1 cell line: an in vitro cell model for immune modulation approach. Int Immunopharmacol, 23(1):37-45.

[9]ColinS, Chinetti-GbaguidiG, StaelsB, 2014. Macrophage phenotypes in atherosclerosis. Immunol Rev, 262(1):153-166.

[10]ChenYB, SongYC, DuW, et al., 2019. Tumor-associated macrophages: an accomplice in solid tumor progression. J Biomed Sci, 26:78.

[11]de MorréeA, FlixB, BagaricI, et al., 2013. Dysferlin regulates cell adhesion in human monocytes. J Biol Chem, 288(20):14147-14157.

[12]DennisG, ShermanBT, HosackDA, et al., 2003. DAVID: database for annotation, visualization, and integrated discovery. Genome Biol, 4(5):3.

[13]di PaoloNC, ShayakhmetovDM, 2016. Interleukin 1α and the inflammatory process. Nat Immunol, 17(8):906-913.

[14]DrazicA, AksnesH, MarieM, et al., 2018. NAA80 is actin’s N-terminal acetyltransferase and regulates cytoskeleton assembly and cell motility. Proc Natl Acad Sci USA, 115(17):4399-4404.

[15]EliginiS, FiorelliS, TremoliE, et al., 2016. Inhibition of transglutaminase 2 reduces efferocytosis in human macrophages: role of CD14 and SR-AI receptors. Nutr Metab Cardiovasc Dis, 26(10):922-930.

[16]EpelmanS, LavineKJ, RandolphGJ, 2014. Origin and functions of tissue macrophages. Immunity, 41(1):21-35.

[17]FerranteCJ, LeibovichSJ, 2012. Regulation of macrophage polarization and wound healing. Adv Wound Care (New Rochelle), 1(1):10-16.

[18]FerranteCJ, Pinhal-EnfieldG, ElsonG, et al., 2013. The adenosine-dependent angiogenic switch of macrophages to an M2-like phenotype is independent of interleukin-4 receptor alpha (IL-4Rα) signaling. Inflammation, 36(4):921-931.

[19]GuoMM, HärtlovaA, GierlińskiM, et al., 2019. Triggering MSR1 promotes JNK-mediated inflammation in IL-4-activated macrophages. EMBO J, 38(11):e100299.

[20]HendricksCM, CordeiroT, GomesAP, et al., 2021. The interplay of HIV-1 and macrophages in viral persistence. Front Microbiol, 12:646447.

[21]HuangC, LewisC, BorgNA, et al., 2018. Proteomic identification of interferon-induced proteins with tetratricopeptide repeats as markers of M1 macrophage polarization. J Proteome Res, 17(4):1485-1499.

[22]HuangX, LiY, FuMG, et al., 2018. Polarizing macrophages in vitro. In: Rousselet G (Ed.), Macrophages: Methods and Protocols. Humana Press, New York, p.119-126.

[23]IvashkivLB, 2018. IFNγ: signalling, epigenetics and roles in immunity, metabolism, disease and cancer immunotherapy. Nat Rev Immunol, 18(9):545-558.

[24]KnudsenE, IversenPO, van RooijenN, et al., 2002. Macrophage-dependent regulation of neutrophil mobilization and chemotaxis during development of sterile peritonitis in the rat. Eur J Haematol, 69(5-6):284-296.

[25]KuoCL, ChouHY, ChiuYC, et al., 2020. Mitochondrial oxidative stress by Lon-PYCR1 maintains an immunosuppressive tumor microenvironment that promotes cancer progression and metastasis. Cancer Lett, 474:138-150.

[26]LeeJ, FrenchB, MorganT, et al., 2014. The liver is populated by a broad spectrum of markers for macrophages. In alcoholic hepatitis the macrophages are M1 and M2. Exp Mol Pathol, 96(1):118-125.

[27]LewisCE, LeekR, HarrisA, et al., 1995. Cytokine regulation of angiogenesis in breast cancer: the role of tumor-associated macrophages. J Leukoc Biol, 57(5):747-751.

[28]LiGM, LiYF, LiuHM, et al., 2020. Genetic heterogeneity of pediatric systemic lupus erythematosus with lymphoproliferation. Medicine (Baltimore), 99(20):e20232.

[29]LiGQ, JinFQ, DuJX, et al., 2019. Macrophage-secreted TSLP and MMP9 promote bleomycin-induced pulmonary fibrosis. Toxicol Appl Pharmacol, 366:10-16.

[30]LiPF, HaoZF, LiuHH, et al., 2021. Quantitative proteomics analysis of berberine-treated colon cancer cells reveals potential therapy targets. Biology, 10(3):250.

[31]LiaoCW, ChouCH, WuXM, et al., 2020. Interleukin-6 plays a critical role in aldosterone-induced macrophage recruitment and infiltration in the myocardium. Biochim Biophys Acta Mol Basis Dis, 1866(3):165627.

[32]LiuYC, ZouXB, ChaiYF, et al., 2014. Macrophage polarization in inflammatory diseases. Int J Biol Sci, 10(5):520-529.

[33]LuJY, CaoQ, ZhengD, et al., 2013. Discrete functions of M2a and M2c macrophage subsets determine their relative efficacy in treating chronic kidney disease. Kidney Int, 84(4):745-755.

[34]MacLeanB, TomazelaDM, ShulmanN, et al., 2010. Skyline: an open source document editor for creating and analyzing targeted proteomics experiments. Bioinformatics, 26(7):966-968.

[35]MartinezFO, HelmingL, MildeR, et al., 2013. Genetic programs expressed in resting and IL-4 alternatively activated mouse and human macrophages: similarities and differences. Blood, 121(9):e57-e69.

[36]MenzelK, HausmannM, ObermeierF, et al., 2006. Cathepsins B, L and D in inflammatory bowel disease macrophages and potential therapeutic effects of cathepsin inhibition in vivo. Clin Exp Immunol, 146(1):169-180.

[37]MinoiaF, TibaldiJ, MuratoreV, et al., 2021. Thrombotic microangiopathy associated with macrophage activation syndrome: a multinational study of 23 patients. J Pediatr, 235:196-202.

[38]MosserDM, EdwardsJP, 2008. Exploring the full spectrum of macrophage activation. Nat Rev Immunol, 8(12):958-969.

[39]MurrayPJ, 2017. Macrophage polarization. Annu Rev Physiol, 79:541-566.

[40]NevenQ, BoulangerC, BruwierA, et al., 2021. Clinical spectrum of Ras-associated autoimmune leukoproliferative disorder (RALD). J Clin Immunol, 41(1):51-58.

[41]NosakaM, IshidaY, KimuraA, et al., 2020. Crucial involvement of IL-6 in thrombus resolution in mice via macrophage recruitment and the induction of proteolytic enzymes. Front Immunol, 10:3150.

[42]OuimetM, EdiriweeraHN, GundraUM, et al., 2015. MicroRNA-33-dependent regulation of macrophage metabolism directs immune cell polarization in atherosclerosis. J Clin Invest, 125(12):4334-4348.

[43]PetersonAC, RussellJD, BaileyDJ, et al., 2012. Parallel reaction monitoring for high resolution and high mass accuracy quantitative, targeted proteomics. Mol Cell Proteomics, 11(11):1475-1488.

[44]ProsperF, VanoverbekeK, StroncekD, et al., 1997. Primitive long-term culture initiating cells (LTC-ICs) in granulocyte colony-stimulating factor mobilized peripheral blood progenitor cells have similar potential for ex vivo expansion as primitive LTC-ICs in steady state bone marrow. Blood, 89(11):3991-3997.

[45]RabinowitzJ, SharifiHJ, MartinH, et al., 2021. xCT/SLC7A11 antiporter function inhibits HIV-1 infection. Virology, 556:149-160.

[46]Shapouri-MoghaddamA, MohammadianS, VaziniH, et al., 2018. Macrophage plasticity, polarization, and function in health and disease. J Cell Physiol, 233(9):6425-6440.

[47]SicaA, MantovaniA, 2012. Macrophage plasticity and polarization: in vivo veritas. J Clin Invest, 122(3):787-795.

[48]SnelB, LehmannG, BorkP, et al., 2000. STRING: a web-server to retrieve and display the repeatedly occurring neighbourhood of a gene. Nucleic Acids Res, 28(18):3442-3444.

[49]SongQQ, HawkinsGA, WudelL, et al., 2019. Dissecting intratumoral myeloid cell plasticity by single cell RNA-seq. Cancer Med, 8(6):3072-3085.

[50]SzklarczykD, FranceschiniA, WyderS, et al., 2015. STRING v10: protein-protein interaction networks, integrated over the tree of life. Nucleic Acids Res, 43(D1):D447-D452.

[51]VagoJP, SugimotoMA, LimaKM, et al., 2019. Plasminogen and the plasminogen receptor, Plg-RKT, regulate macrophage phenotypic, and functional changes. Front Immunol, 10:1458.

[52]WangLX, ZhangSX, WuHJ, et al., 2019. M2b macrophage polarization and its roles in diseases. J Leukoc Biol, 106(2):345-358.

[53]WangQS, NiH, LanL, et al., 2010. Fra-1 protooncogene regulates IL-6 expression in macrophages and promotes the generation of M2d macrophages. Cell Res, 20(6):701-712.

[54]WhiteMJV, GomerRH, 2015. Trypsin, tryptase, and thrombin polarize macrophages towards a pro-fibrotic M2a phenotype. PLoS ONE, 10(9):e0138748.

[55]WuSY, Romero-RamírezL, MeyJ, 2021. Retinoic acid increases phagocytosis of myelin by macrophages. J Cell Physiol, 236(5):3929-3945.

[56]WynnTA, VannellaKM, 2016. Macrophages in tissue repair, regeneration, and fibrosis. Immunity, 44(3):450-462.

[57]WynnTA, ChawlaA, PollardJW, 2013. Macrophage biology in development, homeostasis and disease. Nature, 496(7446):445-455.

[58]ZhaoY, ZhangBZ, ZhangQQ, et al., 2021. Tumor-associated macrophages in osteosarcoma. J Zhejiang Univ-Sci B (Biomed & Biotechnol), 22(11):885-892.

[59]ZizzoG, HilliardBA, MonestierM, et al., 2012. Efficient clearance of early apoptotic cells by human macrophages requires M2c polarization and MerTK induction. J Immunol, 189(7):3508-3520.

Open peer comments: Debate/Discuss/Question/Opinion


Please provide your name, email address and a comment

Journal of Zhejiang University-SCIENCE, 38 Zheda Road, Hangzhou 310027, China
Tel: +86-571-87952783; E-mail: cjzhang@zju.edu.cn
Copyright © 2000 - 2024 Journal of Zhejiang University-SCIENCE