Park Eun-Jung, Yang Mi-Jin, Kang Min-Sung, Jo Young-Min, Yoon Cheolho, Lee Yunseo, Kim Dong-Wan, Lee Gwang-Hee, Kwon Ik-Hwan, Kim Jin-Bae
College of Medicine, Graduate School, Kyung Hee University, 02447, Republic of Korea.
Human Health and Environmental Toxins Research Center, Kyung Hee University, 02447, Republic of Korea.
Toxicol Rep. 2023 Jul 7;11:116-128. doi: 10.1016/j.toxrep.2023.07.002. eCollection 2023 Dec.
Chronic respiratory disease is among the most common non-communicable diseases, and particulate materials (PM) are a major risk factor. Meanwhile, evidence of the relationship between the physicochemical characteristics of PM and pulmonary toxicity mechanism is still limited. Here, we collected particles (CPM) from the air of a port city adjacent to a cement factory, and we found that the CPM contained various elements, including heavy metals (such as arsenic, thallium, barium, and zirconium) which are predicted to have originated from a cement plant adjacent to the sampling site. We also delivered the CPM intratracheally to mice for 13 weeks to investigate the pulmonary toxicity of inhaled CPM. CPM-induced chronic inflammatory lesions with an increased total number of cells in the lung of mice. Meanwhile, among inflammatory mediators measured in this study, levels of IL-1β, TNF-α, CXCL-1, and IFN-γ were elevated in the treated group compared with the controls. Considering that the alveolar macrophage (known as dust cell) is a professional phagocyte that is responsible for the clearance of PM from the respiratory surfaces, we also investigated cellular responses following exposure to CPM in MH-S cells, a mouse alveolar macrophage cell line. CPM inhibited cell proliferation and formed autophagosome-like vacuoles. Intracellular calcium accumulation and oxidative stress, and altered expression of pyrimidine metabolism- and olfactory transduction-related genes were observed in CPM-treated cells. More interestingly, type I-LC3B and full-length PARP proteins were not replenished in CPM-treated cells, and cell cycle changes, apoptotic and necrotic cell death, and caspase-3 cleavage were not significantly detected in cells exposed to CPM. Taken together, we conclude that dysfunction of alveolar macrophages may contribute to CPM-induced pulmonary inflammation. In addition, given the possible transformation of heart tissue observed in CPM-treated mice, we suggest that further study is needed to clarify the systemic pathological changes and the molecular mechanisms following chronic exposure to CPM.
慢性呼吸道疾病是最常见的非传染性疾病之一，颗粒物（PM）是主要危险因素。同时，PM的物理化学特性与肺毒性机制之间关系的证据仍然有限。在此，我们从毗邻水泥厂的港口城市空气中收集颗粒物（CPM），发现CPM含有多种元素，包括重金属（如砷、铊、钡和锆），据推测这些重金属源自采样点附近的水泥厂。我们还将CPM经气管内注射给小鼠13周，以研究吸入CPM的肺毒性。CPM诱导小鼠肺部慢性炎症病变，肺内细胞总数增加。同时，在本研究中检测的炎症介质中，与对照组相比，治疗组中白细胞介素-1β、肿瘤坏死因子-α、CXC趋化因子配体-1和干扰素-γ的水平升高。鉴于肺泡巨噬细胞（即尘细胞）是一种专职吞噬细胞，负责从呼吸表面清除PM，我们还研究了小鼠肺泡巨噬细胞系MH-S细胞暴露于CPM后的细胞反应。CPM抑制细胞增殖并形成自噬体样空泡。在CPM处理的细胞中观察到细胞内钙积累和氧化应激，以及嘧啶代谢和嗅觉转导相关基因表达的改变。更有趣的是，在CPM处理的细胞中，I型微管相关蛋白轻链3B和全长聚ADP核糖聚合酶蛋白没有得到补充，在暴露于CPM的细胞中未显著检测到细胞周期变化、凋亡和坏死性细胞死亡以及半胱天冬酶-3裂解。综上所述，我们得出结论，肺泡巨噬细胞功能障碍可能导致CPM诱导的肺部炎症。此外，鉴于在CPM处理的小鼠中观察到心脏组织可能发生的转变，我们建议需要进一步研究以阐明长期暴露于CPM后的全身病理变化和分子机制。
