Key Laboratory of Drinking Water Science and Technology, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing 100085, China.
University of Chinese Academy of Sciences, Beijing 100049, China.
Environ Sci Technol. 2020 Jul 21;54(14):8900-8908. doi: 10.1021/acs.est.0c01152. Epub 2020 Jul 9.
Scarce attention has been paid to the immunotoxicity of organophosphate flame retardants (PFRs), which poses a challenge to the systematic assessment of their health risks. In this study, a battery of in vitro immunotoxicity screening assays, including adhesion, phagocytosis, and 48 cytokine/chemokine production, was measured after exposing THP-1-derived macrophages to six selected common PFRs (TPHP, TDCPP, TNBP, TOCP, TCEP, and TBOEP) at a noncytotoxic concentration (≤50 μM). Our results showed that TPHP and TBOEP partially attenuated the adhesion and phagocytosis of the THP-1 mφs and that TDCPP caused a functional loss of phagocytosis, implying the potential immunosuppression. In contrast, TNBP and TOCP may cause an immunostimulation by significantly promoting cell adhesion and enhancing phagocytic efficiency. Additionally, the results from a cytokine/chemokine secretion analysis revealed the proinflammatory properties of TDCPP, TPHP, and TBOEP. TOCP was thought to disrupt the inflammatory balance by inhibiting both proinflammatory and antiinflammatory cytokines. TCEP showed no effect on adhesion or phagocytosis and little modulation of cytokine release at this experimental concentration. Overall, this study supports that PFRs can be immunotoxic to macrophages in different ways and provides evidence for developing more sensitive in vitro immunotoxicity bioassay methods.
目前，人们对有机磷阻燃剂（PFRs）的免疫毒性关注较少，这对其健康风险的系统评估提出了挑战。在这项研究中，我们在非细胞毒性浓度（≤50μM）下，用六种常见的 PFRs（TPHP、TDCPP、TNBP、TOCP、TCEP 和 TBOEP）处理 THP-1 衍生的巨噬细胞，检测了一系列体外免疫毒性筛选试验，包括黏附、吞噬作用和 48 种细胞因子/趋化因子的产生。结果表明，TPHP 和 TBOEP 部分削弱了 THP-1 mφs 的黏附和吞噬作用，而 TDCPP 导致吞噬作用功能丧失，提示可能存在免疫抑制作用。相比之下，TNBP 和 TOCP 可能通过显著促进细胞黏附和增强吞噬效率而引起免疫刺激作用。此外，细胞因子/趋化因子分泌分析的结果表明 TDCPP、TPHP 和 TBOEP 具有促炎特性。TOCP 通过抑制促炎和抗炎细胞因子而破坏炎症平衡。在这个实验浓度下，TCEP 对黏附和吞噬作用没有影响，对细胞因子释放的调节作用也很小。总的来说，这项研究支持 PFRs 可以以不同的方式对巨噬细胞产生免疫毒性，并为开发更敏感的体外免疫毒性生物检测方法提供了证据。
