Breidenbach Joshua D, French Benjamin W, Shrestha Upasana, Adya Zaneh K, Wooten R Mark, Fribley Andrew M, Malhotra Deepak, Haller Steven T, Kennedy David J
Department of Medicine, College of Medicine and Life Sciences, University of Toledo, Toledo, OH 43614, USA.
Biochemistry and Biotechnology Group, Bioscience Division, Los Alamos National Laboratory, Los Alamos, NM 87545, USA.
Antioxidants (Basel). 2025 Mar 31;14(4):424. doi: 10.3390/antiox14040424.
Micro- and nanoplastics (MPs and NPs) are pervasive environmental pollutants detected in aquatic ecosystems, with emerging evidence suggesting their presence in airborne particles generated by water body motion. Inhalation exposure to airborne MPs and NPs remains understudied despite documented links between occupational exposure to these particles and adverse respiratory outcomes, including airway inflammation, oxidative stress, and chronic respiratory diseases. This study explored the effects of acute NP exposure on a fully differentiated 3D human airway epithelial model derived from 14 healthy donors. Airway epithelium was exposed to aerosolized 50 nm polystyrene NPs at concentrations ranging from 2.5 to 2500 µg/mL for three minutes per day over three days. Functional assays revealed no significant alterations in tissue integrity, cell survival, mucociliary clearance, or cilia beat frequency, suggesting intact epithelial function post-exposure. However, cytokine and chemokine profiling identified a significant five-fold increase in CCL3 (MIP-1α), a neutrophilic chemoattractant, in NP-exposed samples compared to controls. This was corroborated by increased neutrophil chemotaxis in response to conditioned media from NP-exposed tissues, indicating a pro-inflammatory neutrophilic response. Conversely, levels of interleukins (IL-21, IL-2, IL-15), CXCL10, and TGF-β were significantly reduced, suggesting immunomodulatory effects that may impair adaptive immune responses and tissue repair mechanisms. These findings demonstrate that short-term exposure to NP-containing aerosols induces a distinct pro-inflammatory response in airway epithelium, characterized by enhanced neutrophil recruitment and reduced secretion of key immune modulators. These findings underscore the potential for aerosolized NPs to induce oxidative and inflammatory stress, raising concerns about their long-term impact on respiratory health and redox regulation.
微塑料和纳米塑料（MPs和NPs）是在水生生态系统中检测到的普遍存在的环境污染物，越来越多的证据表明它们存在于水体运动产生的空气中的颗粒物中。尽管有记录表明职业接触这些颗粒物与不良呼吸结果之间存在联系，包括气道炎症、氧化应激和慢性呼吸道疾病，但对空气中MPs和NPs的吸入暴露仍未得到充分研究。本研究探讨了急性NP暴露对源自14名健康供体的完全分化的3D人呼吸道上皮模型的影响。呼吸道上皮每天暴露于浓度范围为2.5至2500μg/mL的雾化50nm聚苯乙烯NP中，持续三天，每天三分钟。功能测定显示组织完整性、细胞存活、黏液纤毛清除或纤毛摆动频率没有显著变化，表明暴露后上皮功能完好。然而，细胞因子和趋化因子分析发现，与对照组相比，NP暴露样本中嗜中性粒细胞趋化因子CCL3（MIP-1α）显著增加了五倍。NP暴露组织的条件培养基诱导的嗜中性粒细胞趋化性增加证实了这一点，表明存在促炎性嗜中性粒细胞反应。相反，白细胞介素（IL-21、IL-2、IL-15）、CXCL10和TGF-β的水平显著降低，表明免疫调节作用可能损害适应性免疫反应和组织修复机制。这些发现表明，短期暴露于含NP的气溶胶会在呼吸道上皮中诱导明显的促炎反应，其特征是嗜中性粒细胞募集增加和关键免疫调节剂的分泌减少。这些发现强调了气溶胶化NP诱导氧化和炎症应激的可能性，引发了人们对其对呼吸健康和氧化还原调节的长期影响的担忧。
