title: Biological effects of particles from the paris subway system.
abstract: 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 microg/cm2 and 5-100 microg/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 alpha (TNFalpha), 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 TNFalpha 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 microg/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.
authors: Inserm, U700 Université Paris 7 Denis Diderot, site Bichat, and Biochimie B, Assistance Publique-Hôpitaux de Paris, Hôpital Bichat, Paris, France.
authors: Rafik
authors: R
authors: Bachoual
authors: Jorge
authors: J
authors: Boczkowski
authors: Delphine
authors: D
authors: Goven
authors: Nadia
authors: N
authors: Amara
authors: Lyes
authors: L
authors: Tabet
authors: Dinhill
authors: D
authors: On
authors: Véronique
authors: V
authors: Leçon-Malas
authors: Michel
authors: M
authors: Aubier
authors: Sophie
authors: S
authors: Lanone
mesh_terms: D000280:Administration, Inhalation; D000393:Air Pollutants / Q000633:toxicity*; D000818:Animals; D001980:Bronchi / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D001992:Bronchoalveolar Lavage Fluid; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D002947:Cities; D017364:Collagenases / Q000235:genetics / Q000378:metabolism*; D016207:Cytokines / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004784:Environmental Monitoring / Q000379:methods; D015870:Gene Expression / Q000187:drug effects; D006419:Heme Oxygenase (Decyclizing) / Q000235:genetics / Q000378:metabolism; D019570:Inhalation Exposure; D008264:Macrophages / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009504:Neutrophils / Q000187:drug effects / Q000473:pathology; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology; D052638:Particulate Matter / Q000633:toxicity*; D011890:Railroads; D019714:Tissue Inhibitor of Metalloproteinases / Q000235:genetics / Q000378:metabolism
chemical_list: D000393:Air Pollutants; D016207:Cytokines; D052638:Particulate Matter; D019714:Tissue Inhibitor of Metalloproteinases; D006419:Heme Oxygenase (Decyclizing); D017364:Collagenases