Biological Effects of Particles from the Paris Subway System

• Published in: Chemical research in toxicology 2007-10, Vol.20 (10), p.1426-1433
• Main Authors: Bachoual, Rafik, Boczkowski, Jorge, Goven, Delphine, Amara, Nadia, Tabet, Lyes, On, Dinhill, Leçon-Malas, Véronique, Aubier, Michel, Lanone, Sophie
• Format: Article
• Language: English
• Subjects: Administration, Inhalation; Air Pollutants - toxicity; Animals; Bronchi - drug effects; Bronchi - metabolism; Bronchi - pathology; Bronchoalveolar Lavage Fluid; Cell Line; Cell Survival - drug effects; Cities; Collagenases - genetics; Collagenases - metabolism; Cytokines - metabolism; Dose-Response Relationship, Drug; Environmental Monitoring - methods; Gene Expression - drug effects; Heme Oxygenase (Decyclizing) - genetics; Heme Oxygenase (Decyclizing) - metabolism; Inhalation Exposure; Macrophages - drug effects; Macrophages - metabolism; Male; Mice; Mice, Inbred C57BL; Neutrophils - drug effects; Neutrophils - pathology; Oxidative Stress - drug effects; Oxidative Stress - physiology; Particulate Matter - toxicity; Railroads; Tissue Inhibitor of Metalloproteinases - genetics; Tissue Inhibitor of Metalloproteinases - metabolism
• ISSN: 0893-228X; 1520-5010
• DOI: 10.1021/tx700093j

Particulate matter (PM) from atmospheric pollution can easily deposit in the lungs and induce recruitment of inflammatory cells, a source of inflammatory cytokines, oxidants, and matrix metalloproteases (MMPs), which are important players in lung structural homeostasis. In many large cities, the subway system is a potent source of PM emission, but little is known about the biological effects of PM from this source. We performed a comprehensive study to evaluate the biological effects of PM sampled at two sites (RER and Metro) in the Paris subway system. Murine macrophages (RAW 264.7) and C57Bl/6 mice, respectively, were exposed to 0.01–10 µg/cm2 and 5–100 µg/mouse subway PM or reference materials [carbon black (CB), titanium dioxide (TiO2), or diesel exhaust particles (DEPs)]. We analyzed cell viability, production of cellular and lung proinflammatory cytokines [tumor necrosis factor α (TNFα), macrophage inflammatory protein (MIP-2), KC (the murin analog of interleukin-8), and granulocyte macrophage-colony stimulating factor (GM-CSF)], and mRNA or protein expression of MMP-2, -9, and -12 and heme oxygenase-1 (HO-1). Deferoxamine and polymixin B were used to evaluate the roles of iron and endotoxin, respectively. Noncytotoxic concentrations of subway PM (but not CB, TiO2, or DEPs) induced a time- and dose-dependent increase in TNFα and MIP-2 production by RAW 264.7 cells, in a manner involving, at least in part, PM iron content (34% inhibition of TNF production 8 h after stimulation of RAW 264.7 cells with 10 µg/cm2 RER particles pretreated with deferoxamine). Similar increased cytokine production was transiently observed in vivo in mice and was accompanied by an increased neutrophil cellularity of bronchoalveolar lavage (84.83 ± 0.98% of polymorphonuclear neutrophils for RER-treated mice after 24 h vs 7.33 ± 0.99% for vehicle-treated animals). Subway PM induced an increased expression of MMP-12 and HO-1 both in vitro and in vivo. PM from the Paris subway system has transient biological effects. Further studies are needed to better understand the pathophysiological implications of these findings.