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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.

Original publication

DOI

10.1177/0271678x17710182

Type

Journal article

Journal

Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism

Publication Date

08/2017

Volume

37

Pages

2679 - 2690

Addresses

1 Division of Brain Sciences, Department of Medicine Hammersmith Hospital, Imperial College London, London, UK.

Keywords

Brain, Microglia, Cells, Cultured, Macrophages, Myeloid Cells, Animals, Mice, Inbred C57BL, Humans, Acetamides, Pyridines, Lipopolysaccharides, Granulocyte-Macrophage Colony-Stimulating Factor, Receptors, GABA, Species Specificity, Gene Expression, Protein Binding, Adult, Middle Aged, Interferon-gamma, Young Adult