According to the World Health Organization (WHO), air pollution is one of the most serious threats for our planet. Despite a growing public awareness of the harmful effects of air pollution on human health, the specific influence of particulate matter (PM) on human immune cells remains poorly understood. In this study, we investigated the effect of PM on peripheral blood monocytes in vitro. Monocytes from healthy donors (HD) were exposed to two types of PM: NIST (SRM 1648a, standard urban particulate matter from the US National Institute for Standards and Technology) and LAP (SRM 1648a with the organic fraction removed). The exposure to PM-induced mitochondrial ROS production followed by the decrease of mitochondrial membrane potential and activation of apoptotic protease activating factor 1 (Apaf-1), Caspase-9, and Caspase-3, leading to the cleavage of Gasdermin E (GSDME), and initiation of pyroptosis. Further analysis showed a simultaneous PM-dependent activation of inflammasomes, including NLRP3 (nucleotide-binding oligomerization domain-like receptor pyrin domain containing 3) and Caspase-1, followed by cleavage of Gasdermin D (GSDMD) and secretion of IL-1β. These observations suggest that PM-treated monocytes die by pyroptosis activated by two parallel signaling pathways, related to the inorganic and organic PM components. The release of IL-1β and expression of danger-associated molecular patterns (DAMPs) by pyroptotic cells further activated the remnant viable monocytes to produce inflammatory cytokines (TNF-α, IL-6, IL-8) and protected them from death induced by the second challenge with PM. In summary, our report shows that PM exposure significantly impacts monocyte function and induces their death by pyroptosis. Our observations indicate that the composition of PM plays a crucial role in this process—the inorganic fraction of PM is responsible for the induction of the Caspase-3-dependent pyroptotic pathway. At the same time, the canonical inflammasome path is activated by the organic components of PM, including LPS (Lipopolysaccharide/endotoxin).

中文翻译：

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空气污染通过激活炎症小体和 Caspase-3 依赖性途径诱导人类单核细胞焦亡

根据世界卫生组织（WHO）的说法，空气污染是地球面临的最严重的威胁之一。尽管公众越来越意识到空气污染对人类健康的有害影响，但颗粒物 (PM) 对人体免疫细胞的具体影响仍知之甚少。在本研究中，我们在体外研究了 PM 对外周血单核细胞的影响。来自健康供体 (HD) 的单核细胞暴露于两种类型的 PM：NIST（SRM 1648a，美国国家标准与技术研究所的标准城市颗粒物）和 LAP（去除有机部分的 SRM 1648a）。暴露于 PM 诱导的线粒体 ROS 产生后，线粒体膜电位降低，凋亡蛋白酶激活因子 1 (Apaf-1)、Caspase-9 和 Caspase-3 被激活，导致 Gasdermin E (GSDME) 裂解，并引发细胞焦亡。进一步的分析显示，炎症小体同时发生 PM 依赖性激活，包括 NLRP3（核苷酸结合寡聚化结构域样受体，含有热蛋白结构域 3）和 Caspase-1，随后裂解 Gasdermin D (GSDMD) 并分泌 IL-1β。这些观察结果表明，经 PM 处理的单核细胞会因与无机和有机 PM 成分相关的两条平行信号通路激活的细胞焦亡而死亡。焦亡细胞释放 IL-1β 并表达危险相关分子模式 (DAMP)，进一步激活残余的存活单核细胞产生炎性细胞因子 (TNF-α、IL-6、IL-8)，并保护它们免遭死亡诱导的死亡。与 PM 的第二个挑战。总之，我们的报告表明，PM 暴露显着影响单核细胞功能并诱导其因细胞焦亡而死亡。我们的观察表明，PM 的组成在此过程中起着至关重要的作用——PM 的无机部分负责诱导 Caspase-3 依赖性焦亡途径。同时，PM 的有机成分（包括 LPS（脂多糖/内毒素））会激活典型的炎症小体路径。