Air pollution drives macrophage senescence through a phagolysosome-15-lipoxygenase pathway.
Air pollution drives macrophage senescence through a phagolysosome-15-lipoxygenase pathway.
复制标题
空气污染通过吞噬溶酶体 15-脂氧合酶途径驱动巨噬细胞衰老。
DOI：
10.1101/2024.01.04.574228
复制
发表时间：
2024
期刊：
影响因子：
--
通讯作者：
Lajoie,Stephane
中科院分区：
文献类型：
--
作者：
Thomas,SarahA;Yong,HwanMee;Rule,AnaM;Gour,Naina;Lajoie,Stephane
城市颗粒物（PM；uPM）会带来严重的健康风险，特别是对呼吸系统。细颗粒物，例如PM2.5。 5、可以深入肺部并加剧一系列健康问题，包括肺气肿、哮喘和肺癌。 PM 暴露还与心脏和神经退行性疾病等肺外疾病有关。此外，长期暴露在PM2.5水平升高的环境中会降低整体预期寿命。衰老是一种功能失调的细胞状态，通常与年龄相关，但也可能由环境压力因素促成。本研究旨在确定 uPM 是否可以驱动巨噬细胞衰老，巨噬细胞是参与颗粒吞噬介导清除的重要细胞类型。尽管已知 uPM 暴露会损害免疫功能，但这种缺陷是多方面的且尚未完全了解，部分原因是使用柴油机尾气颗粒等颗粒物作为真正 uPM 的替代品。 uPM 是从美国的多个地点收集的，包括巴尔的摩、休斯顿和菲尼克斯。用 uPM 或参考颗粒（例如柴油机尾气颗粒）刺激骨髓来源的巨噬细胞，以评估衰老相关参数。我们报道，暴露于 uPM 的骨髓源性巨噬细胞呈现衰老表型，其特征是 IL-1α 分泌增加、衰老相关的 β-半乳糖苷酶活性和增殖减弱。暴露于过敏原未能引起这种反应，这支持了不同类型的环境暴露之间的区别。 uPM 诱导的衰老与关键的巨噬细胞激活途径无关，特别是炎症小体和清道夫受体。然而，吞噬溶酶体途径的抑制消除了衰老标记，支持该表型归因于 uPM 吞噬作用。这些数据表明，uPM 暴露会导致巨噬细胞衰老，这可能有助于免疫病理学。
Urban particulate matter (PM; uPM) poses significant health risks, particularly to the respiratory system. Fine particles, such as PM2. 5, can penetrate deep into the lungs and exacerbate a range of health problems, including emphysema, asthma, and lung cancer. PM exposure is also linked to extrapulmonary disorders such as heart and neurodegenerative diseases. Moreover, prolonged exposure to elevated PM levels can reduce overall life expectancy. Senescence is a dysfunctional cell state typically associated with age but can also be precipitated by environmental stressors. This study aimed to determine whether uPM could drive senescence in macrophages, an essential cell type involved in particulate phagocytosis-mediated clearance. Although it is known that uPM exposure impairs immune function, this deficit is multifaceted and incompletely understood, partly because of the use of particulates such as diesel exhaust particles as a surrogate for true uPM. uPM was collected from several locations in the United States, including Baltimore, Houston, and Phoenix. Bone marrow–derived macrophages were stimulated with uPM or reference particulates (eg, diesel exhaust particles) to assess senescence-related parameters. We report that uPM-exposed bone marrow–derived macrophages adopt a senescent phenotype characterized by increased IL-1α secretion, senescence-associated β-galactosidase activity, and diminished proliferation. Exposure to allergens failed to elicit such a response, supporting a distinction between different types of environmental exposure. uPM-induced senescence was independent of key macrophage activation pathways, specifically inflammasome and scavenger receptors. However, inhibition of the phagolysosome pathway abrogated senescence markers, supporting this phenotype’s attribution to uPM phagocytosis. These data suggest that uPM exposure leads to macrophage senescence, which may contribute to immunopathology.