title: Comparative acute lung inflammation induced by atmospheric PM and size-fractionated tire particles.
abstract: A comparison of the effects produced by size-fractionated tire particles (TP10 and TP2.5) and similar-sized urban particulate matter (PM10 and PM2.5), collected in Milan in 2007, on the lungs of mice has been performed. The focus is on early acute lung responses following intratracheal instillation of aerosolized particles at a 3-h recovery period. Together with bronchoalveolar lavage (BAL) conventional endpoints like total and differential cell counts, total protein, alkaline phosphatase, lactate dehydrogenase and pro-inflammatory cytokines (TNF-alpha, MIP-2), the expression of different stress protein markers (caspase8, Hsp70, H0-1, NF-kB) was evaluated 3h after particle instillation into Balb/c mice. The TP2.5 fraction reached the alveolar spaces and produced an acute inflammatory response as evidenced by increased LDH and AP activities, total protein and Hsp70 content. TNF-alpha and MIP-2 production was significantly increased and polymorphonuclear neutrophils (PMN) recruitment was apparent. The TP10 fraction distributed mainly in the bronchial district and the only modified BAL parameter was the expression of MIP-2. PM2.5 induced an inflammatory response lesser in magnitude than that produced by PM10 fraction. The TNF-alpha increase was not significant, and HO-1, though significantly increased with respect to the control, was unable to reduce NF-kB activation, suggesting a role of the endotoxin component of PM in stimulating a pro-inflammatory limited response. This response was maximized by the PM10 that induced a significant increase in MIP-2, TNF-alpha, and HO-1. Lung immunohistochemistry showed fine particles, TPs in particular, being able to deeply penetrate and rapidly induce inflammatory events in the parenchyma, even involving endothelial cells, while PM10 produced a strong pro-inflammatory response mediated by the bronchiolar cells and residential macrophages of the proximal alveolar sacs, likely as a consequence of its larger dimension and endotoxin content. These results provide evidence of variable inflammatory mechanisms in mouse lungs in response to both urban PM and tire particles.
authors.affiliation: Department of Environmental Science, POLARIS Research Center, University of Milano-Bicocca, 1 piazza della Scienza, Milan 20126, Italy. paride.mantecca@unimib.it
authors.forename: Paride
authors.initials: P
authors.lastname: Mantecca
authors.forename: Francesca
authors.initials: F
authors.lastname: Farina
authors.forename: Elisa
authors.initials: E
authors.lastname: Moschini
authors.forename: Daniele
authors.initials: D
authors.lastname: Gallinotti
authors.forename: Maurizio
authors.initials: M
authors.lastname: Gualtieri
authors.forename: Annette
authors.initials: A
authors.lastname: Rohr
authors.forename: Giulio
authors.initials: G
authors.lastname: Sancini
authors.forename: Paola
authors.initials: P
authors.lastname: Palestini
authors.forename: Marina
authors.initials: M
authors.lastname: Camatini
mesh_terms: D000208:Acute Disease; D000388:Air / Q000032:analysis* / Q000592:standards; D000393:Air Pollutants / Q000633:toxicity*; D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D015415:Biomarkers / Q000032:analysis; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry / Q000166:cytology / Q000276:immunology; D016207:Cytokines / Q000378:metabolism; D007442:Intubation, Intratracheal; D008168:Lung / Q000187:drug effects* / Q000201:enzymology / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D018384:Oxidative Stress / Q000187:drug effects; D010316:Particle Size; D052638:Particulate Matter / Q000633:toxicity*; D011014:Pneumonia / Q000139:chemically induced* / Q000201:enzymology / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D012117:Resins, Synthetic / Q000737:chemistry*
chemical_list: D000393:Air Pollutants; D000975:Antioxidants; D015415:Biomarkers; D016207:Cytokines; D052638:Particulate Matter; D012117:Resins, Synthetic