Co-exposure of ferruginous components of subway particles with lipopolysaccharide impairs vascular function: A comparative study with ambient particulate matter

• Published in: Ecotoxicology and environmental safety 2024-12, Vol.288, p.117356, Article 117356
• Main Authors: Owokoniran, Oluwatoyin Hannah, Honda, Akiko, Ichinose, Takamichi, Ishikawa, Raga, Nagao, Megumi, Miyasaka, Natsuko, Wang, Zaoshi, Takai, Satsuki, Omori, Issei, Zhang, Kerui, Liu, Wei, Higaki, Yuya, Kameda, Takayuki, Matsuda, Tomonari, Fujiwara, Taku, Okuda, Tomoaki, Takano, Hirohisa
• Format: Article
• Language: English
• Subjects: Aerosols; Air Pollutants - toxicity; Animals; Cell Survival - drug effects; Cytokines - metabolism; environmental pollutants; Ferric Compounds - toxicity; Human Umbilical Vein Endothelial Cells - drug effects; Humans; inflammation induction; innate immune response; Lipopolysaccharide; Lipopolysaccharides; Mice; Particle Size; Particulate Matter - toxicity; particulate matter exposure; Plasminogen Activator Inhibitor 1 - metabolism; Railroads; vascular dysfunction; Vehicle Emissions - toxicity
• ISSN: 0147-6513; 1090-2414; 1090-2414
• DOI: 10.1016/j.ecoenv.2024.117356

Several empirical studies have linked subway and ambient particle exposure to toxicity, pro-inflammatory responses, and vascular dysfunction. However, the health effects of pollutants generated from varying sources, particularly when combined with lipopolysaccharide (LPS), are still unexplored. Therefore, the aim of this study was to investigate the characteristic health effects of iron oxide particles (the main components of subway particles) in comparison with urban aerosols (UA) and vehicle exhaust particles (VEP), alone and in combination with LPS. This study revealed that iron oxides caused a more significant reduction in human umbilical vein endothelial cell viability, increased lactate dehydrogenase release, and decreased the production of plasminogen activator inhibitor-1, a fibrinolytic modulator, and endothelin-1, a vasoconstrictor, compared to those by VEP and UA at marginally toxic and toxic concentrations. While VEP and UA induced an increase in interleukin (IL)-6 production, iron oxides, particularly Fe3O4, increased IL-8 production at slightly toxic and non-cytotoxic concentrations. In addition, co-exposure of all particles and LPS at non-cytotoxic concentrations promoted pro-inflammatory cytokine (IL-6 and IL-8) production relative to exposure to the particles alone. Interestingly, the tendency towards either coagulation or fibrinolytic conditions was dependent on the concentration of exposed particles at the same LPS concentration. Furthermore, increases in inflammation, neutrophil and lymphocyte recruitment around blood vessels, and edema were observed in murine lungs exposed to a combination of iron oxides and LPS compared to those in mice exposed to iron oxide alone. Thus, iron oxide-rich subway particulate poses more health risks than outdoor ambient particles since they can significantly impair endothelial function, particularly through gross cellular and vascular homeostatic protein damage, and induce exacerbated inflammatory responses during co-exposure. These findings provide novel empirical evidence for epidemiological studies seeking mechanisms responsible for the observed health impact of transport- and occupational-related exposures on vascular dysfunction. [Display omitted] •Vascular function was assessed after LPS, iron oxides and ambient particle exposure.•Iron oxides caused toxicity, inflammation and impaired key vascular proteins.•Non-cytotoxic iron oxides impaired vascular proteins relative to ambient particles.•LPS promo