Macrophage Extracellular Traps Suppress Particulate Matter–Induced Airway Inflammation

IF 4.7 2区 医学 Q1 PATHOLOGY
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引用次数: 0

Abstract

Accumulating evidence has substantiated the potential of ambient particulate matter (PM) to elicit detrimental health consequences in the respiratory system, notably airway inflammation. Macrophages, a pivotal component of the innate immune system, assume a crucial function in responding to exogenous agents. However, the roles and detailed mechanisms in regulating PM-induced airway inflammation remain unclear. The current study revealed that PM had the ability to stimulate the formation of macrophage extracellular traps (METs) both in vitro and in vivo. This effect was dependent on peptidylarginine deiminase type 4 (PAD4)–mediated histone citrullination. Additionally, reactive oxygen species were involved in the formation of PM-induced METs, in parallel with PAD4. Genetic deletion of PAD4 in macrophages resulted in an up-regulation of inflammatory cytokine expression. Moreover, mice with PAD4-specific knockout in myeloid cells exhibited exacerbated PM-induced airway inflammation. Mechanistically, inhibition of METs suppressed the phagocytic ability in macrophages, leading to airway epithelial injuries and an aggravated PM-induced airway inflammation. The present study demonstrates that METs play a crucial role in promoting the phagocytosis and clearance of PM by macrophages, thereby suppressing airway inflammation. Furthermore, it suggests that activation of METs may represent a novel therapeutic strategy for PM-related airway disorders.

巨噬细胞胞外捕获器可抑制颗粒物诱发的气道炎症。
越来越多的证据证明,环境颗粒物(PM)有可能对呼吸系统造成有害健康的后果,尤其是气道炎症。巨噬细胞是先天性免疫系统的重要组成部分,在对外源物质做出反应时发挥着关键作用。然而,调节 PM 诱导的气道炎症的作用和详细机制仍不清楚。我们的研究发现,可吸入颗粒物能够在体外和体内刺激巨噬细胞胞外陷阱(MET)的形成。这种作用依赖于 PAD4 介导的组蛋白瓜氨酸化。此外,还发现活性氧与 PAD4 同时参与了 PM 诱导的 MET 的形成。在巨噬细胞中遗传性删除 PAD4 会导致炎症细胞因子表达上调。此外,在骨髓细胞中特异性敲除 PAD4 的小鼠表现出 PM 诱导的气道炎症加剧。从机理上讲,抑制 METs 可抑制巨噬细胞的吞噬能力,导致气道上皮损伤和 PM 诱导的气道炎症加重。本研究表明,METs 在促进巨噬细胞吞噬和清除 PM,从而抑制气道炎症方面起着至关重要的作用。此外,研究还表明,激活 METs 可能是治疗 PM 相关气道疾病的一种新策略。
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来源期刊
CiteScore
11.40
自引率
0.00%
发文量
178
审稿时长
30 days
期刊介绍: The American Journal of Pathology, official journal of the American Society for Investigative Pathology, published by Elsevier, Inc., seeks high-quality original research reports, reviews, and commentaries related to the molecular and cellular basis of disease. The editors will consider basic, translational, and clinical investigations that directly address mechanisms of pathogenesis or provide a foundation for future mechanistic inquiries. Examples of such foundational investigations include data mining, identification of biomarkers, molecular pathology, and discovery research. Foundational studies that incorporate deep learning and artificial intelligence are also welcome. High priority is given to studies of human disease and relevant experimental models using molecular, cellular, and organismal approaches.
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