Department of Pharmacology and Toxicology, Center for Research on Ingredient Safety, Institute for Integrative Toxicology, Michigan State University, East Lansing, Michigan, USA.
Department of Environmental Health Sciences, Robert Stempel College of Public Health & Social Work, Florida International University, Miami, Florida, USA.
J Leukoc Biol. 2021 Jul;110(1):123-140. doi: 10.1002/JLB.3A1219-729RR. Epub 2020 Nov 17.
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 ∆ -tetrahydrocannabinol. These findings suggest that cell surface TSPO in circulating leukocytes could serve as a peripheral blood-based biomarker of inflammation.
转位蛋白 18kDa（TSPO）是一种众所周知的线粒体外膜蛋白，它被广泛用作神经炎症和脑损伤的生物标志物。虽然人们认为 TSPO 在许多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、活性氧生成和增殖，但这些功能中的一些最近受到了质疑。在这里，我们报告了一个意外的发现，即循环免疫细胞在其细胞表面上差异表达基础水平的 TSPO，其中高比例的单核细胞和中性粒细胞表达细胞表面 TSPO。体外用 LPS 刺激单核细胞会显著增加表面 TSPO 表达细胞的频率，而不改变基因表达。重要的是，单核细胞中 LPS 诱导的 TSPO 细胞表面表达增加似乎是 LPS 特有的，因为另外两种不同的单核细胞激活剂未能增加表面 TSPO 表达细胞的频率。最后，当我们在接受抗逆转录病毒治疗的 HIV 供体（一种慢性炎症性疾病）中定量检测免疫细胞 TSPO 表面表达时，我们发现 TSPO 表面定位的频率显著增加，这种增加可以用 ∆-四氢大麻酚进行药理学抑制。这些发现表明，循环白细胞中的细胞表面 TSPO 可以作为炎症的外周血生物标志物。
