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Surface translocator protein 18 kDa (TSPO) localization on immune cells upon stimulation with LPS and in ART-treated HIV+ subjects
Journal of Leukocyte Biology ( IF 5.5 ) Pub Date : 2020-11-17 , DOI: 10.1002/jlb.3a1219-729rr
Lance K Blevins 1 , Robert B Crawford 1 , Diana J Azzam 2 , Tomás R Guilarte 2 , Norbert E Kaminski 1
Affiliation  

Translocator protein 18 kDa (TSPO) is a well-known outer mitochondrial membrane protein and it is widely used as a biomarker of neuroinflammation and brain injury. Although it is thought that TSPO plays key roles in a multitude of host cell functions, including steroid biosynthesis, apoptosis, generation of reactive oxygen species, and proliferation, some of these functions have recently been questioned. Here, we report the unexpected finding that circulating immune cells differentially express basal levels of TSPO on their cell surface, with a high percentage of monocytes and neutrophils expressing cell surface TSPO. In vitro stimulation of monocytes with LPS significantly increases the frequency of cells with surface TSPO expression in the absence of altered gene expression. Importantly, the LPS increase in TSPO cell surface expression in monocytes appears to be selective for LPS because two other distinct monocyte activators failed to increase the frequency of cells with surface TSPO. Finally, when we quantified immune cell TSPO surface expression in antiretroviral therapy-treated HIV+ donors, a chronic inflammatory disease, we found significant increases in the frequency of TSPO surface localization, which could be pharmacologically suppressed with ∆9-tetrahydrocannabinol. These findings suggest that cell surface TSPO in circulating leukocytes could serve as a peripheral blood-based biomarker of inflammation.

中文翻译:

表面易位蛋白 18 kDa (TSPO) 在 LPS 刺激和 ART 治疗的 HIV+ 受试者中定位于免疫细胞

Translocator protein 18 kDa (TSPO) 是一种众所周知的线粒体外膜蛋白,被广泛用作神经炎症和脑损伤的生物标志物。尽管人们认为 TSPO 在多种宿主细胞功能中发挥关键作用,包括类固醇生物合成、细胞凋亡、活性氧物质的产生和增殖,但其中一些功能最近受到质疑。在这里,我们报告了一个意想不到的发现,即循环免疫细胞在其细胞表面差异表达基础水平的 TSPO,其中高百分比的单核细胞和中性粒细胞表达细胞表面 TSPO。在没有改变基因表达的情况下,用 LPS 体外刺激单核细胞显着增加了具有表面 TSPO 表达的细胞的频率。重要的,单核细胞中 TSPO 细胞表面表达的 LPS 增加似乎对 LPS 具有选择性,因为另外两种不同的单核细胞活化剂未能增加具有表面 TSPO 的细胞的频率。最后,当我们量化抗逆转录病毒疗法治疗的 HIV 中的免疫细胞 TSPO 表面表达时+供体,一种慢性炎症性疾病,我们发现 TSPO 表面定位的频率显着增加,这可以通过 Δ 9 -四氢大麻酚在药理学上得到抑制。这些发现表明,循环白细胞中的细胞表面 TSPO 可以作为基于外周血的炎症生物标志物。
更新日期:2020-11-17
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