Laboratory of DDS Design and Drug Disposition, Graduate School of Pharmaceutical Sciences, Tohoku University, Sendai, 980-8578, Japan.
Graduate School of Engineering, Kyoto University, Kyoto, 615-8530, Japan.
Sci Rep. 2024 May 7;14(1):10503. doi: 10.1038/s41598-024-61255-4.
Diesel exhaust particles (DEPs) are very small (typically < 0.2 μm) fragments that have become major air pollutants. DEPs are comprised of a carbonaceous core surrounded by organic compounds such as polycyclic aromatic hydrocarbons (PAHs) and nitro-PAHs. Inhaled DEPs reach the deepest sites in the respiratory system where they could induce respiratory/cardiovascular dysfunction. Additionally, a previous study has revealed that a portion of inhaled DEPs often activate immune cells and subsequently induce somatic inflammation. Moreover, DEPs are known to localize in lymph nodes. Therefore, in this study we explored the effect of DEPs on the lymphatic endothelial cells (LECs) that are a constituent of the walls of lymph nodes. DEP exposure induced cell death in a reactive oxygen species (ROS)-dependent manner. Following exposure to DEPs, next-generation sequence (NGS) analysis identified an upregulation of the integrated stress response (ISR) pathway and cell death cascades. Both the soluble and insoluble components of DEPs generated intracellular ROS. Three-dimensional Raman imaging revealed that DEPs are taken up by LECs, which suggests internalized DEP cores produce ROS, as well as soluble DEP components. However, significant cell death pathways such as apoptosis, necroptosis, ferroptosis, pyroptosis, and parthanatos seem unlikely to be involved in DEP-induced cell death in LECs. This study clarifies how DEPs invading the body might affect the lymphatic system through the induction of cell death in LECs.
柴油机排气颗粒物（DEPs）是非常小的（通常<0.2μm）碎片，已成为主要的空气污染物。DEPs 由一个碳质核心组成，周围环绕着有机化合物，如多环芳烃（PAHs）和硝基-PAHs。吸入的 DEPs 到达呼吸系统的最深部位，在那里它们可能引起呼吸/心血管功能障碍。此外，先前的一项研究表明，一部分吸入的 DEPs 经常激活免疫细胞，随后诱导体细胞炎症。此外，DEPs 已知定位于淋巴结。因此，在这项研究中，我们探讨了 DEPs 对构成淋巴结壁的淋巴管内皮细胞（LECs）的影响。DEP 暴露以活性氧（ROS）依赖性方式诱导细胞死亡。暴露于 DEPs 后，下一代测序（NGS）分析鉴定出整合应激反应（ISR）途径和细胞死亡级联的上调。DEP 的可溶性和不溶性成分都产生了细胞内 ROS。三维拉曼成像显示 DEPs 被 LECs 摄取，这表明内化的 DEP 核心产生 ROS，以及可溶性 DEP 成分。然而，凋亡、坏死性凋亡、铁死亡、细胞焦亡和 Parthanatos 等显著的细胞死亡途径似乎不太可能参与 LECs 中 DEP 诱导的细胞死亡。本研究阐明了侵入人体的 DEPs 如何通过诱导 LECs 细胞死亡来影响淋巴系统。
