The DOI matches its Crossref record; 61 of the 61 references it cites were found in a registry or an index.
Pro-inflammatory activation of primary microglia and macrophages increases 18 kDa translocator protein expression in rodents but not humans
Open accessAbstract
The 18kDa Translocator Protein (TSPO) is the most commonly used tissue-specific marker of inflammation in positron emission tomography (PET) studies. It is expressed in myeloid cells such as microglia and macrophages, and in rodent myeloid cells expression increases with cellular activation. We assessed the effect of myeloid cell activation on TSPO gene expression in both primary human and rodent microglia and macrophages in vitro, and also measured TSPO radioligand binding with 3 H-PBR28 in primary human macrophages. As observed previously, we found that TSPO expression increases (∼9-fold) in rodent-derived macrophages and microglia upon pro-inflammatory stimulation. However, TSPO expression does not increase with classical pro-inflammatory activation in primary human microglia (fold change 0.85 [95% CI 0.58–1.12], p = 0.47). In contrast, pro-inflammatory activation of human monocyte-derived macrophages is associated with a reduction of both TSPO gene expression (fold change 0.60 [95% CI 0.45–0.74], p = 0.02) and TSPO binding site abundance (fold change 0.61 [95% CI 0.49–0.73], p < 0.0001). These findings have important implications for understanding the biology of TSPO in activated macrophages and microglia in humans. They are also clinically relevant for the interpretation of PET studies using TSPO targeting radioligands, as they suggest changes in TSPO expression may reflect microglial and macrophage density rather than activation phenotype.
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“Recently, we have shown in vitro that, although TSPO gene and protein expression and TSPO radioligand binding increases in rodent microglia and macrophages with inflammatory stimulation, relative TSPO gene expression in human microglia and TSPO ligand binding in human monocyte-derived macrophages are reduced with pro-inflammatory activation (Owen et al., 2017).”
From A quantitative neuropathological assessment of translocator protein expression in multiple sclerosis (2019) · cites this paper as Owen et al., 2017
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“Recently, we have shown in vitro that, although TSPO gene and protein expression and TSPO radioligand binding increases in rodent microglia and macrophages with inflammatory stimulation, relative TSPO gene expression in human microglia and TSPO ligand binding in human monocyte-derived macrophages are reduced with pro-inflammatory activation (Owen et al., 2017).”
From A quantitative neuropathological assessment of translocator protein expression in multiple sclerosis (2019) · cites this paper as Owen et al., 2017
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“However, in humans, TSPO is not upregulated in either pro-inflammatory macrophages (Narayan et al., 2017) or primary microglia (Owen et al., 2017).”
From A quantitative neuropathological assessment of translocator protein expression in multiple sclerosis (2019) · cites this paper as Owen et al., 2017
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“This new observation thus confirms in vitro data suggesting that the TSPO expression signal does not distinguish between microglial phenotypes in human tissue (Owen et al., 2017).”
From A quantitative neuropathological assessment of translocator protein expression in multiple sclerosis (2019) · cites this paper as Owen et al., 2017
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Cites
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Selenica, M.-L. B., Brownlow, M., Jimenez, J. P., Lee, D. C., Pena, G., Dickey, C. A., Gordon, M. N., & Morgan, D. (2013) · Neurodegenerative Diseases · doi:10.1159/000337230 · Cited by 10,359
Identification of a unique TGF-β–dependent molecular and functional signature in microglia
Butovsky, O., Jedrychowski, M. P., Moore, C. S., Cialic, R., Lanser, A. J., Gabriely, G., Koeglsperger, T., Dake, B., Wu, P. M., Doykan, C. E., et al. (2014) · Nature Neuroscience · doi:10.1038/nn.3599 · Cited by 2,543 · cited 1×
“Furthermore, many of the markers with differential expression profiles in human microglia relative to human macrophages are not expressed by rodent myeloid cells.(37,38) Our findings add to these differences and suggest that extrapolating TSPO biology from rodent to human myeloid cells should be done with extreme caut…”
BackgroundSelf-citationMitochondrial reactive oxygen species trigger hypoxia-induced transcription
Chandel, N. S., Maltepe, E., Goldwasser, E., Mathieu, C. E., Simon, M. C., & Schumacker, P. T. (1998) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.95.20.11715 · Cited by 1,926
Microglial physiology: unique stimuli, specialized responses
Ransohoff, R. M., & Perry, V. H. (2009) · Annual Review of Immunology · doi:10.1146/annurev.immunol.021908.132528 · Cited by 1,858 · cited 3×
“Microglia also express receptors for neurotransmitters including g-aminobutyric acid (GABA) and glutamate, providing another pathway for microglial phenotypic regulation.(1,50,51) Caution should therefore be used when extrapolating these findings in vivo and further work will therefore examine directly how TSPO expres…”
BackgroundInnate immune activation in neurodegenerative disease
Heneka, M. T., Kummer, M. P., & Latz, E. (2014) · Nature Reviews Immunology · doi:10.1038/nri3705 · Cited by 1,437 · cited 3×
“Dysregulated or inappropriate microglial activation is thought to contribute to many neurodegenerative diseases.(4) Modulating microglial phenotype has therefore been hypothesised as a potential therapeutic strategy for diseases such as Alzheimer’s and Parkinson’s Disease.”
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Wolf, S. A., Boddeke, H. W. G. M., & Kettenmann, H. (2017) · Annual Review of Physiology · doi:10.1146/annurev-physiol-022516-034406 · Cited by 1,426 · cited 1×
“Rodent microglia are used extensively given the scarcity of primary human microglia; however, there are several important differences between the two cell types.(34,35) For example, in rodent but not human microglia, transforming growth Figure 2.”
In vivo imaging of microglial activation with [11C](R)-PK11195 PET in idiopathic Parkinson's disease
Gerhard, A., Pavese, N., Hotton, G., Turkheimer, F., Es, M., Hammers, A., Eggert, K., Oertel, W., Banati, R. B., & Brooks, D. J. (2006) · Neurobiology of Disease · doi:10.1016/j.nbd.2005.08.002 · Cited by 1,200
Owen, D. R., Yeo, A. J., Gunn, R. N., Song, K., Wadsworth, G., Lewis, A., Rhodes, C., Pulford, D. J., Bennacef, I., Parker, C. A., et al. (2012) · Journal of Cerebral Blood Flow & Metabolism · doi:10.1038/jcbfm.2011.147 · Cited by 779
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“At confluency, cultures were subjected to mild trypsinization as described.(32) Following removal of the astrocyte monolayer, microglia were re-plated at a density of 2 10(5) cells mL 1 in DMEMþ 10% FBS, 100 U mL 1 penicillin and 100 mg mL 1 streptomycin Owen et al.”
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“It is, however, important to note that the expression of TSPO initially thought to represent microglia activation, has been recently proposed to also measure local myeloid cell proliferation, or monocytes infiltration (Owen et al., 2017).”
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“immune challenges induce TSPO upregulation in anti-inflammatory M2-like macrophages, and TSPO reduction in inflammatory M1-like macrophages (Narayan et al., 2017; Owen et al., 2017).”
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Metadata
- Authors
- Owen, D. R., Narayan, N., Wells, L., Healy, L., Smyth, E., Rabiner, E. A., Galloway, D., Williams, J. B., Lehr, J., Mandhair, H., Peferoen, L. A., Taylor, P. C., Amor, S., Antel, J. P., Matthews, P. M., & Moore, C. S.
- Affiliations
- Hammersmith Hospital (GB)
- University of Oxford (GB)
- Montreal Neurological Institute and Hospital (CA)
- King's College London (GB)
- Memorial University of Newfoundland (CA)
- Vrije Universiteit Amsterdam (NL)
- Queen Mary University of London (GB)
- Corresponding author
- Owen, David R
- ORCID
- Venue
- Journal of Cerebral Blood Flow & Metabolism
- Publisher
- SAGE Publications
- Published
- 2017-05-22
- Volume
- 37
- Issue
- 8
- Pages
- 2679-2690
- ISSN
- 0271-678X (ISSN-L)
- 1559-7016
- PMC
- PMC5536262
- OpenAlex
- W2619298813
- Cited by
- 194
- References
- 61
- Citations by year
- 2026: 10 · 2025: 12 · 2024: 22 · 2023: 25 · 2022: 26 · 2021: 24 · 2020: 35 · 2019: 18 · 2018: 17 · 2017: 5
- FWCI
- 10.22
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Locations
- Journal of Cerebral Blood Flow & Metabolism (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Research Portal (King's College London) (publishedVersion, other-oa)
- Amsterdam UMC (VU Amsterdam) - Institutional Repository (publishedVersion)
- Pure Amsterdam UMC (submittedVersion, cc-by)
- Spiral (Imperial College London) (submittedVersion, other-oa)
- Data Archiving and Networked Services (DANS) (submittedVersion)
- Funders
- National Institute for Health and Care Research (NF-SI-0514-10022)
- Multiple Sclerosis Society
- Canadian Institutes of Health Research
- Medical Research Council (MR/N008219/1, MR/N026934/1)
- Topics
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmacology › Pharmacological Receptor Mechanisms and Effects
- Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Medical Imaging Techniques and Applications
- Keywords
- TSPO, microglia, macrophages, pro-inflammatory activation, myeloid cell activation, monocyte-derived macrophages
- MeSH terms
- Acetamides, Adult, Animals, Brain, Cells, Cultured, Humans, Interferon-gamma, Lipopolysaccharides, Macrophages, Mice, Inbred C57BL, Middle Aged, Protein Binding, Pyridines, Species Specificity, Gene Expression, Granulocyte-Macrophage Colony-Stimulating Factor, Microglia, Receptors, GABA, Myeloid Cells, Young Adult
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