The macrophage marker translocator protein (TSPO) is down-regulated on pro-inflammatory ‘M1’ human macrophages

PLoS ONE

Volumn 12, Issue 10, 2017, Pages

  Narayan, Nehal ^a   Mandhair, Harpreet ^a   Smyth, Erica ^b   Dakin, Stephanie Georgina ^a   Kiriakidis, Serafim ^a   Wells, Lisa ^b   Owen, David ^c   Sabokbar, Afsie ^a   Taylor, Peter ^a  

^a UNIVERSITY OF OXFORD   (United Kingdom)

^b Imanova Ltd   (United Kingdom)

^c IMPERIAL COLLEGE LONDON   (United Kingdom)

Author keywords

[No Author keywords available]

Indexed keywords

DEXAMETHASONE; INTERLEUKIN 4; MEMBRANE PROTEIN; MESSENGER RNA; PROTEIN TSPO; TRANSFORMING GROWTH FACTOR BETA1; UNCLASSIFIED DRUG; 4 AMINOBUTYRIC ACID RECEPTOR; GAMMA INTERFERON; LIPOPOLYSACCHARIDE; TSPO PROTEIN, HUMAN;

ADULT; ARTICLE; BLOOD CELL; CELL DIFFERENTIATION; CELL STIMULATION; CLINICAL ARTICLE; DOWN REGULATION; ENZYME LINKED IMMUNOSORBENT ASSAY; FEMALE; HUMAN; HUMAN CELL; IMMUNOFLUORESCENCE TEST; MACROPHAGE ACTIVATION; MALE; MONOCYTE; PHENOTYPE; PROTEIN EXPRESSION; REAL TIME POLYMERASE CHAIN REACTION; RHEUMATOID ARTHRITIS; SYNOVIAL FLUID; THP-1 CELL LINE; UPREGULATION; WESTERN BLOTTING; CELL LINE; GENETICS; INFLAMMATION; MACROPHAGE; METABOLISM; POSITRON EMISSION TOMOGRAPHY;

ARTHRITIS, RHEUMATOID; CELL LINE; DOWN-REGULATION; HUMANS; INFLAMMATION; INTERFERON-GAMMA; INTERLEUKIN-4; LIPOPOLYSACCHARIDES; MACROPHAGES; MONOCYTES; POSITRON-EMISSION TOMOGRAPHY; REAL-TIME POLYMERASE CHAIN REACTION; RECEPTORS, GABA; RNA, MESSENGER;

EID: 85030257645     PISSN: None     EISSN: 19326203     Source Type: Journal    
DOI: 10.1371/journal.pone.0185767     Document Type: Article

References (67)

1. Batarseh A, Papadopoulos V. Regulation of translocator protein 18 kDa (TSPO) expression in health and disease states. Mol Cell Endocrinol. 2010; 327(1–2):1–12. https://doi.org/10.1016/j.mce.2010.06.013 PMID: 20600583
2. Papadopoulos V, Lecanu L, Brown RC, Han Z, Yao ZX. Peripheral-type benzodiazepine receptor in neurosteroid biosynthesis, neuropathology and neurological disorders. Neuroscience. 2006; 138 (3):749–56. https://doi.org/10.1016/j.neuroscience.2005.05.063 PMID: 16338086
3. Vowinckel E, Reutens D, Becher B, Verge G, Evans A, Owens T, et al. PK11195 binding to the peripheral benzodiazepine receptor as a marker of microglia activation in multiple sclerosis and experimental autoimmune encephalomyelitis. J Neurosci Res. 1997; 50(2):345–53. https://doi.org/10.1002/(SICI)1097-4547(19971015)50:2<345::AID-JNR22>3.0.CO;2-5 PMID: 9373043
4. van der Laken CJ, Elzinga EH, Kropholler MA, Molthoff CF, van der Heijden JW, Maruyama K, et al. Noninvasive imaging of macrophages in rheumatoid synovitis using 11C-(R)-PK11195 and positron emission tomography. Arthritis Rheum. 2008; 58(11):3350–5. https://doi.org/10.1002/art.23955 PMID: 18975347
5. Gent YY, Weijers K, Molthoff CF, Windhorst AD, Huisman MC, Kassiou M, et al. Promising potential of new generation translocator protein tracers providing enhanced contrast of arthritis imaging by positron emission tomography in a rat model of arthritis. Arthritis Res Ther. 2014; 16(2):R70. https://doi.org/10.1186/ar4509 PMID: 24625077
6. Navegantes KC, de Souza Gomes R, Pereira PAT, Czaikoski PG, Azevedo CHM, Monteiro MC. Immune modulation of some autoimmune diseases: the critical role of macrophages and neutrophils in the innate and adaptive immunity. J Transl Med. 2017; 15:36. https://doi.org/10.1186/s12967-017-1141-8 PMID: 28202039
7. Hume DA. The Many Alternative Faces of Macrophage Activation. Front Immunol. 2015; 6:370. https://doi.org/10.3389/fimmu.2015.00370 PMID: 26257737
8. Sica A, Mantovani A. Macrophage plasticity and polarization: in vivo veritas. J Clin Invest. 2012; 122 (3):787–95. https://doi.org/10.1172/JCI59643 PMID: 22378047
9. Murray PJ, Wynn TA. Protective and pathogenic functions of macrophage subsets. Nat Rev Immunol. 2011; 11(11):723–37. https://doi.org/10.1038/nri3073 PMID: 21997792
10. Murray PJ, Allen JE, Biswas SK, Fisher EA, Gilroy DW, Goerdt S, et al. Macrophage activation and polarization: nomenclature and experimental guidelines. Immunity. 2014; 41(1):14–20. https://doi.org/10.1016/j.immuni.2014.06.008 PMID: 25035950
11. Martinez FO, Gordon S. The M1 and M2 paradigm of macrophage activation: time for reassessment. F1000prime Rep. 2014; 6:13. https://doi.org/10.12703/P6-13 PMID: 24669294
12. Bonsack Ft, Alleyne CH Jr., Sukumari-Ramesh S. Augmented expression of TSPO after intracerebral hemorrhage: a role in inflammation? J Neuroinflammation. 2016; 13(1):151. https://doi.org/10.1186/s12974-016-0619-2 PMID: 27315802
13. Shao X, Wang X, English SJ, Desmond T, Sherman PS, Quesada CA, et al. Imaging of carrageenan-induced local inflammation and adjuvant-induced systemic arthritis with [(11)C]PBR28 PET. Nucl Med Biol. 2013; 40(7):906–11. https://doi.org/10.1016/j.nucmedbio.2013.06.008 PMID: 23891203
14. Murray PJ, Wynn TA. Obstacles and opportunities for understanding macrophage polarization. J Leukoc Biol. 2011; 89(4):557–63. https://doi.org/10.1189/jlb.0710409 PMID: 21248152
15. Schneemann M, Schoeden G. Macrophage biology and immunology: man is not a mouse. J Leukoc Biol. 2007; 81(3):579; discussion 80. https://doi.org/10.1189/jlb.1106702 PMID: 17332373
16. Mestas J, Hughes CC. Of mice and not men: differences between mouse and human immunology. J Immunol. 2004; 172(5):2731–8. PMID: 14978070
17. Thomas AC, Mattila JT. “Of Mice and Men”: Arginine Metabolism in Macrophages. Front Immunol. 2014; 5:479. https://doi.org/10.3389/fimmu.2014.00479 PMID: 25339954
18. Raes G, Van den Bergh R, De Baetselier P, Ghassabeh GH, Scotton C, Locati M, et al. Arginase-1 and Ym1 are markers for murine, but not human, alternatively activated myeloid cells. J Immunol. 2005; 174 (11):6561; author reply -2. PMID: 15905489
19. Lawrence T, Natoli G. Transcriptional regulation of macrophage polarization: enabling diversity with identity. Nat Rev Immunol. 2011; 11(11):750–61. https://doi.org/10.1038/nri3088 PMID: 22025054
20. Schneemann M, Schoedon G. Species differences in macrophage NO production are important. Nat Immunol. 2002; 3(2):102. https://doi.org/10.1038/ni0202-102a PMID: 11812978
21. Mosser DM, Edwards JP. Exploring the full spectrum of macrophage activation. Nat Rev Immunol. 8 (12):958–969. https://doi.org/10.1038/nri2448 PMID: 19029990
22. Auwerx J. The human leukemia cell line, THP-1: a multifacetted model for the study of monocyte-macrophage differentiation. Experientia. 1991; 47(1):22–31. PMID: 1999239
23. Stroncek DF, Fellowes V, Pham C, Khuu H, Fowler DH, Wood LV, et al. Counter-flow elutriation of clinical peripheral blood mononuclear cell concentrates for the production of dendritic and T cell therapies. J Transl Med. 2014; 12:241. https://doi.org/10.1186/s12967-014-0241-y PMID: 25223845
24. Berger TG, Strasser E, Smith R, Carste C, Schuler-Thurner B, Kaempgen E, et al. Efficient elutriation of monocytes within a closed system (Elutra) for clinical-scale generation of dendritic cells. J Immunol Methods. 2005; 298(1–2):61–72. https://doi.org/10.1016/j.jim.2005.01.005 PMID: 15847797
25. Yasaka T, Mantich NM, Boxer LA, Baehner RL. Functions of human monocyte and lymphocyte subsets obtained by countercurrent centrifugal elutriation: differing functional capacities of human monocyte subsets. J Immunol. 1981; 127(4):1515–8. PMID: 6268707
26. Schwanke U, Nabereit A, Moog R. Isolation of monocytes from whole blood-derived buffy coats by continuous counter-flow elutriation. J Clin Apher. 2006; 21(3):153–7. https://doi.org/10.1002/jca.20077 PMID: 16395728
27. Banfalvi G. Cell cycle synchronization of animal cells and nuclei by centrifugal elutriation. Nat Protoc. 2008; 3(4):663–73. https://doi.org/10.1038/nprot.2008.34 PMID: 18388949
28. Aletaha D, Neogi T, Silman AJ, Funovits J, Felson DT, Bingham CO 3rd, et al. 2010 Rheumatoid arthritis classification criteria: an American College of Rheumatology/European League Against Rheumatism collaborative initiative. Arthritis Rheum. 2010; 62(9):2569–81. https://doi.org/10.1002/art.27584 PMID: 20872595
29. Martinez FO. Analysis of gene expression and gene silencing in human macrophages. Curr Protoc Immunol. 2012;Chapter 14:Unit 14.28.1–3.
30. Liu H, Shi B, Huang C-C, Eksarko P, Pope RM. Transcriptional diversity during monocyte to macrophage differentiation. Immunol Lett. 2008; 117(1):70–80. https://doi.org/10.1016/j.imlet.2007.12.012 PMID: 18276018
31. Frede S, Stockmann C, Freitag P, Fandrey J. Bacterial lipopolysaccharide induces HIF-1 activation in human monocytes via p44/42 MAPK and NF-kappaB. Biochem J. 2006; 396(3):517–27. https://doi.org/10.1042/BJ20051839 PMID: 16533170
32. Krausgruber T, Blazek K, Smallie T, Alzabin S, Lockstone H, Sahgal N, et al. IRF5 promotes inflammatory macrophage polarization and TH1-TH17 responses. Nat Immunol. 2011; 12(3):231–8. https://doi.org/10.1038/ni.1990 PMID: 21240265
33. Han J, Hajjar DP, Tauras JM, Feng J, Gotto AM Jr., Nicholson AC. Transforming growth factor-beta1 (TGF-beta1) and TGF-beta2 decrease expression of CD36, the type B scavenger receptor, through mitogen-activated protein kinase phosphorylation of peroxisome proliferator-activated receptor-gamma. J Biol Chem. 2000; 275(2):1241–6. PMID: 10625669
34. Dakin SG, Martinez FO, Yapp C, Wells G, Oppermann U, Dean BJF, et al. Inflammation activation and resolution in human tendon disease. Sci Transl Med. 2015; 7(311):311ra173–311ra173. https://doi.org/10.1126/scitranslmed.aac4269 PMID: 26511510
35. Martinez FO, Gordon S, Locati M, Mantovani A. Transcriptional profiling of the human monocyte-to-macrophage differentiation and polarization: new molecules and patterns of gene expression. J Immunol. 2006; 177(10):7303–11. PMID: 17082649
36. Roszer T. Understanding the mysterious M2 macrophage through activation markers and effector mechanisms. Mediators Inflamm. 2015; 2015:816460. https://doi.org/10.1155/2015/816460 PMID: 26089604
37. Koning N, van Eijk M, Pouwels W, Brouwer MS, Voehringer D, Huitinga I, et al. Expression of the inhibitory CD200 receptor is associated with alternative macrophage activation. J Innate Imm. 2010; 2 (2):195–200.
38. Taylor SC, Berkelman T, Yadav G, Hammond M. A defined methodology for reliable quantification of Western blot data. Mol Biotechnol. 2013; 55(3):217–26. https://doi.org/10.1007/s12033-013-9672-6 PMID: 23709336
39. Chauveau F, Boutin H, Van Camp N, Dolle F, Tavitian B. Nuclear imaging of neuroinflammation: a comprehensive review of [11C]PK11195 challengers. Eur J Nucl Med Mol Imaging. 2008; 35(12):2304–19. https://doi.org/10.1007/s00259-008-0908-9 PMID: 18828015
40. Oh U, Fujita M, Ikonomidou VN, Evangelou IE, Matsuura E, Harberts E, et al. Translocator protein PET imaging for glial activation in multiple sclerosis. J Neuroimmune Pharmacol. 2011; 6(3):354–61. https://doi.org/10.1007/s11481-010-9243-6 PMID: 20872081
41. Nair A, Veronese M, Xu X, Curtis C, Turkheimer F, Howard R, et al. Test-retest analysis of a non-invasive method of quantifying [(11)C]-PBR28 binding in Alzheimer’s disease. EJNMMI Res. 2016; 6(1):72. https://doi.org/10.1186/s13550-016-0226-3 PMID: 27678494
42. Owen DR, Yeo AJ, Gunn RN, Song K, Wadsworth G, Lewis A, et al. An 18-kDa translocator protein (TSPO) polymorphism explains differences in binding affinity of the PET radioligand PBR28. J Cereb Blood Flow Metab. 2012; 32(1):1–5. https://doi.org/10.1038/jcbfm.2011.147 PMID: 22008728
43. Owen DR, Howell OW, Tang SP, Wells LA, Bennacef I, Bergstrom M, et al. Two binding sites for [3H] PBR28 in human brain: implications for TSPO PET imaging of neuroinflammation.J Cereb Blood Flow Metab. 2010; 30(9):1608–18. https://doi.org/10.1038/jcbfm.2010.63 PMID: 20424634
44. Canat X, Carayon P, Bouaboula M, Cahard D, Shire D, Roque C, et al. Distribution profile and properties of peripheral-type benzodiazepine receptors on human hemopoietic cells. Life Sci. 1993; 52 (1):107–18. PMID: 8380214
45. Wynn TA, Chawla A, Pollard JW. Origins and Hallmarks of Macrophages: Development, homeostasis, and disease. Nature. 2013; 496(7446):445–55. https://doi.org/10.1038/nature12034 PMID: 23619691
46. Kennedy A, Fearon U, Veale DJ, Godson C. Macrophages in synovial Inflammation. Front Immunol 2011; 2:52. https://doi.org/10.3389/fimmu.2011.00052 PMID: 22566842
47. Mulherin D, Fitzgerald O, Bresnihan B. Synovial tissue macrophage populations and articular damage in rheumatoid arthritis. Arthritis Rheum. 1996; 39(1):115–24. PMID: 8546720
48. Gent YY, Voskuyl AE, Kloet RW, van Schaardenburg D, Hoekstra OS, Dijkmans BA, et al. Macrophage positron emission tomography imaging as a biomarker for preclinical rheumatoid arthritis: findings of a prospective pilot study. Arthritis Rheum. 2012; 64(1):62–6. https://doi.org/10.1002/art.30655 PMID: 21898356
49. Gent YY, Ahmadi N, Voskuyl AE, Hoetjes N, van Kuijk C, Britsemmer K, et al. Detection of subclinical synovitis with macrophage targeting and positron emission tomography in patients with rheumatoid arthritis without clinical arthritis. J Rheumatol. 2014; 41(11):2145–52. https://doi.org/10.3899/jrheum.140059 PMID: 25274888
50. Sandiego CM, Gallezot JD, Pittman B, Nabulsi N, Lim K, Lin SF, et al. Imaging robust microglial activation after lipopolysaccharide administration in humans with PET. Proc Natl Acad Sci U S A. 2015; 112 (40):12468–73. https://doi.org/10.1073/pnas.1511003112 PMID: 26385967
51. Garcia-Cabezas MA, John YJ, Barbas H, Zikopoulos B. Distinction of Neurons, Glia and Endothelial Cells in the Cerebral Cortex: An Algorithm Based on Cytological Features. Front Neuroanat. 2016; 10:107. https://doi.org/10.3389/fnana.2016.00107 PMID: 27847469
52. Ransohoff RM, Kivisakk P, Kidd G. Three or more routes for leukocyte migration into the central nervous system. Nat Rev Immunol. 2003; 3(7):569–81. https://doi.org/10.1038/nri1130 PMID: 12876559
53. Scarf AM, Kassiou M. The translocator protein. J Nucl Med. 2011; 52(5):677–80. https://doi.org/10.2967/jnumed.110.086629 PMID: 21498529
54. Morin D, Musman J, Pons S, Berdeaux A, Ghaleh B. Mitochondrial translocator protein (TSPO): From physiology to cardioprotection. Biochem Pharmacol. 2016; 105:1–13. https://doi.org/10.1016/j.bcp.2015.12.003 PMID: 26688086
55. Ching AS, Kuhnast B, Damont A, Roeda D, Tavitian B, Dolle F. Current paradigm of the 18-kDa translocator protein (TSPO) as a molecular target for PET imaging in neuroinflammation and neurodegenera-tive diseases. Insights Imaging. 2012; 3(1):111–9. https://doi.org/10.1007/s13244-011-0128-x PMID: 22696004
56. Banks WA, Gray AM, Erickson MA, Salameh TS, Damodarasamy M, Sheibani N, et al. Lipopolysaccharide-induced blood-brain barrier disruption: roles of cyclooxygenase, oxidative stress, neuroinflammation, and elements of the neurovascular unit. J Neuroinflamm. 2015; 12:223.
57. Davies LC, Jenkins SJ, Allen JE, Taylor PR. Tissue-resident macrophages. Nat Immunol. 2013; 14 (10):986–95. https://doi.org/10.1038/ni.2705 PMID: 24048120
58. Bae KR, Shim HJ, Balu D, Kim SR, Yu SW. Translocator protein 18 kDa negatively regulates inflammation in microglia. J Neuroimmune Pharmacol. 2014; 9(3):424–37. https://doi.org/10.1007/s11481-014-9540-6 PMID: 24687172
59. Allen AM, Taylor JM, Graham A. Mitochondrial (dys)function and regulation of macrophage cholesterol efflux. Clin Sci. 2013; 124(8):509–15. https://doi.org/10.1042/CS20120358 PMID: 23298226
60. Fessler MB, Parks JS. Intracellular lipid flux and membrane microdomains as organizing principles in inflammatory cell signaling. J Immunol. 2011; 187(4):1529–35. https://doi.org/10.4049/jimmunol.1100253 PMID: 21810617
61. Chowdhury SM, Zhu X, Aloor JJ, Azzam KM, Gabor KA, Ge W, et al. Proteomic Analysis of ABCA1-Null Macrophages Reveals a Role for Stomatin-Like Protein-2 in Raft Composition and Toll-Like Receptor Signaling. Mol Cell Proteomics. 2015; 14(7):1859–70. https://doi.org/10.1074/mcp.M114.045179 PMID: 25910759
62. Niyonzima N, Samstad EO, Aune MH, Ryan L, Bakke SS, Rokstad AM, et al. Reconstituted High-Density Lipoprotein Attenuates Cholesterol Crystal-Induced Inflammatory Responses by Reducing Complement Activation. J Immunol. 2015; 195(1):257–64. https://doi.org/10.4049/jimmunol.1403044 PMID: 26026058
63. Taylor JM, Allen AM, Graham A. Targeting mitochondrial 18 kDa translocator protein (TSPO) regulates macrophage cholesterol efflux and lipid phenotype. Clin Sci. 2014; 127(10):603–13. https://doi.org/10.1042/CS20140047 PMID: 24814875
64. Lamare F, Hinz R, Gaemperli O, Pugliese F, Mason JC, Spinks T, et al. Detection and quantification of large-vessel inflammation with 11C-(R)-PK11195 PET/CT. J Nucl Med. 2011; 52(1):33–9. https://doi.org/10.2967/jnumed.110.079038 PMID: 21149475
65. Park E, Gallezot JD, Delgadillo A, Liu S, Planeta B, Lin SF, et al. (11)C-PBR28 imaging in multiple sclerosis patients and healthy controls: test-retest reproducibility and focal visualization of active white matter areas. Eur J Nucl Med Mol Imaging. 2015; 42(7):1081–92. https://doi.org/10.1007/s00259-015-3043-4 PMID: 25833352
66. Schweitzer PJ, Fallon BA, Mann JJ, Kumar JS. PET tracers for the peripheral benzodiazepine receptor and uses thereof. Drug Discov Today. 2010; 15(21–22):933–42. https://doi.org/10.1016/j.drudis.2010.08.012 PMID: 20800696
67. Bernards N, Pottier G, Theze B, Dolle F, Boisgard R. In vivo evaluation of inflammatory bowel disease with the aid of muPET and the translocator protein 18 kDa radioligand [18F]DPA-714. Mol Imaging Biol. 2015; 17(1):67–75. https://doi.org/10.1007/s11307-014-0765-9 PMID: 25015387