Pro-inflammatory activation of primary microglia and macrophages increases 18 kDa translocator protein expression in rodents but not humans.
Pro-inflammatory activation of primary microglia and macrophages increases 18 kDa translocator protein expression in rodents but not humans.
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DOI：
10.1177/0271678x17710182
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发表时间：
2017-08
期刊：
影响因子：
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通讯作者：
Moore CS
中科院分区：
文献类型：
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作者：
Owen DR;Narayan N;Wells L;Healy L;Smyth E;Rabiner EA;Galloway D;Williams JB;Lehr J;Mandhair H;Peferoen LA;Taylor PC;Amor S;Antel JP;Matthews PM;Moore CS
18kDa 易位蛋白 (TSPO) 是正电子发射断层扫描 (PET) 研究中最常用的炎症组织特异性标记物。它在小胶质细胞和巨噬细胞等骨髓细胞中表达，并且在啮齿动物骨髓细胞中表达随着细胞激活而增加。我们在体外评估了骨髓细胞活化对原代人类和啮齿动物小胶质细胞和巨噬细胞中 TSPO 基因表达的影响，并测量了原代人类巨噬细胞中 TSPO 放射性配体与 3H-PBR28 的结合。正如之前所观察到的，我们发现在促炎刺激下，啮齿类动物源性巨噬细胞和小胶质细胞中 TSPO 表达增加（〜9 倍）。然而，在原代人小胶质细胞中，TSPO 表达并不随着经典促炎症激活而增加（倍数变化 0.85 [95% CI 0.58–1.12]，p = 0.47）。相反，人类单核细胞来源的巨噬细胞的促炎激活与 TSPO 基因表达（倍数变化 0.60 [95% CI 0.45–0.74]，p = 0.02）和 TSPO 结合位点丰度（倍数变化 0.61 [95% CI 0.49–0.73]，p< 0.0001）的减少相关。这些发现对于理解人类活化巨噬细胞和小胶质细胞中 TSPO 的生物学具有重要意义。它们在临床上也与使用 TSPO 靶向放射性配体的 PET 研究的解释相关，因为它们表明 TSPO 表达的变化可能反映小胶质细胞和巨噬细胞密度而不是激活表型。
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.