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J Cereb Blood Flow Metab. 2017 Aug;37(8):2679-2690. doi: 10.1177/0271678X17710182. Epub 2017 May 22.

Pro-inflammatory activation of primary microglia and macrophages increases 18 kDa translocator protein expression in rodents but not humans.

Author information

1
1 Division of Brain Sciences, Department of Medicine Hammersmith Hospital, Imperial College London, London, UK.
2
2 Nuffield Department of Orthopaedics, Rheumatology & Musculoskeletal Sciences, Botnar Research Centre, University of Oxford, Oxford, UK.
3
3 Imanova Centre for Imaging Science, Hammersmith Hospital, London, UK.
4
4 Neuroimmunology Unit, Montreal Neurological Institute, McGill University, Montreal, Quebec, Canada.
5
5 Centre for Neuroimaging Sciences, King's College, London, UK.
6
6 Division of Biomedical Sciences, Faculty of Medicine, Memorial University of Newfoundland, St. John's, Newfoundland.
7
7 Pathology Department, VU Medical Centre, VU University of Amsterdam, The Netherlands.
8
8 Neuroimmunology Unit, Blizard Institute, Barts and the London School of medicine & Dentistry Queen Mary University of London, UK.
9
9 UK Dementia Research Institute, Imperial College London, London, UK.

Abstract

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 3H-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.

KEYWORDS:

Positron emission tomography; inflammation; macrophages; microglia; neurodegeneration

PMID:
28530125
PMCID:
PMC5536262
DOI:
10.1177/0271678X17710182
[Indexed for MEDLINE]
Free PMC Article

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