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1.
Inhal Toxicol ; 20(14): 1215-31, 2008 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-18855153

RESUMO

Inflammation is regarded as an important mechanism in mortality and morbidity associated with exposures of cardiorespiratory patients to urban air particulate matter. We investigated the association of the chemical composition and sources of urban air fine (PM(2.5-0.2)) and coarse (PM(10-2.5)) particulate samples with the inflammatory activity in the mouse lung. The particulate samples were collected during selected seasons in six European cities using a high-volume cascade impactor. Healthy C57BL/6J mice were intratracheally instilled with a single dose (10 mg/kg) of the particulate samples. At 4, 12, and 24 h after the exposure, the lungs were lavaged and the bronchoalveolar lavage fluid (BALF) was assayed for indicators of inflammation and tissue damage: cell number, total protein, and cytokines (tumor necrosis factor [TNF]-alpha, interleukin [IL]-6, and KC). Dicarboxylic acids and transition metals, especially Ni and V, in PM(2.5-0.2) correlated positively and some secondary inorganic ions (NO3(-), NH4(+)) negatively with the inflammatory activity. Total organic matter and SO4(2-) had no consistent correlations. In addition, the soil-derived constituents (Ca2+, Al, Fe, Si) showed positive correlations with the PM(2.5-0.2)-induced inflammatory activity, but their role in PM(10-2.5) remained obscure, possibly due to largely undefined biogenic material. Markers of poor biomass and coal combustion, i.e., monosaccharide anhydrides and As, were associated with elevated PAH contents in PM(2.5-0.2) and a consistent immunosuppressive effect. Overall, our results support epidemiological findings that the local sources of incomplete combustion and resuspended road dust are important in urban air particulate pollution-related health effects.


Assuntos
Poluentes Atmosféricos/efeitos adversos , Poluentes Atmosféricos/química , Tamanho da Partícula , Material Particulado/efeitos adversos , Material Particulado/química , Poluição do Ar , Animais , Europa (Continente) , Óleos Combustíveis/efeitos adversos , Masculino , Metais/efeitos adversos , Metais/química , Camundongos , Camundongos Endogâmicos C57BL , Compostos Orgânicos/efeitos adversos , Compostos Orgânicos/química , Emissões de Veículos
2.
Inhal Toxicol ; 19(3): 213-25, 2007 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-17365026

RESUMO

We investigated the cytotoxic and inflammatory activities of size-segregated particulate samples (particulate matter, PM) from contrasting air pollution situations in Europe. Coarse (PM10-2.5), fine (PM2.5-0.2), and ultrafine (PM0.2) particulate samples were collected with a modified Harvard high-volume cascade impactor (HVCI). Mouse RAW 264.7 macrophages were exposed to the samples for 24 h. Selected inflammatory mediators, nitric oxide (NO) and cytokines (tumor necrosis factor alpha [TNFalpha], interleukin 6 [IL-6], macrophage inflammatory protein-2 [MIP-2]), were measured together with cytotoxicity (MTT test), and analysis of apoptosis and cell cycle (propidium iodide staining). The PM10-2.5 samples had a much higher inflammatory activity than the PM2.5-0.2 and PM0.2 samples, but the PM2.5-0.2 samples showed the largest differences in inflammatory activity, and the PM0.2 samples in cytotoxicity, between the sampling campaigns. The PM2.5-0.2 samples from traffic environments in springtime Barcelona and summertime Athens had the highest inflammatory activities, which may be related to the high photochemical activity in the atmosphere during the sampling campaigns. The PM0.2 sample from wintertime Prague with proven impacts from local coal and biomass combustion had very high cytotoxic and apoptotic activities and caused a distinct cell cycle arrest. Thus, particulate size, sources, and atmospheric transformation processes affect the toxicity profile of urban air particulate matter. These factors may explain some of the heterogeneity observed in particulate exposure-response relationships of human health effects in epidemiological studies.


Assuntos
Poluentes Atmosféricos/toxicidade , Inflamação/induzido quimicamente , Macrófagos/efeitos dos fármacos , Material Particulado/toxicidade , Animais , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Citocinas/biossíntese , Camundongos , Óxido Nítrico/biossíntese , Tamanho da Partícula
3.
Scand J Work Environ Health ; 30 Suppl 2: 80-90, 2004.
Artigo em Inglês | MEDLINE | ID: mdl-15487689

RESUMO

OBJECTIVES: The chemical composition and toxicity of wintertime urban-air particulate matter with an aerodynamic diameter of <10 microm (PM10), derived mostly from long-range transport and local combustion sources, were compared with those of springtime PM10 derived mostly from the resuspension of road dust. METHODS: Water-soluble ions and elements and polycyclic aromatic hydrocarbons (PAH) were analyzed from seasonally pooled PM10 samples collected at a busy traffic site in Helsinki in 1999. These PM10 samples were also tested for cytotoxicity [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide test] and the production of proinflammatory cytokines [tumor necrosis factor alpha (TNF-alpha) and interleukin 6 (IL-6)] and nitric oxide (NO) in the mouse macrophage cell line RAW 264.7. Their oxidative capacity and the associated DNA (deoxyribonucleic acid) damage were investigated by electron paramagnetic resonance and the formation of 8-hydroxy-2'-deoxyguanosine (8-OH-DG) in isolated calf thymus DNA, respectively. RESULTS: The late wintertime and springtime PM10 had similar compositions of water-soluble ions and elements, but the winter PM10 had a higher content of PAH. The spring PM10 was a much more potent inducer of TNF-alpha and IL-6 production than the winter PM10 was, but there were no consistent differences in cytotoxic potency. In contrast, the winter PM10 was a significantly more potent inducer of NO production and 8-OH-DG formation. The large cytokine responses to the spring PM10 were caused by its insoluble fraction and largely inhibited by the endotoxin antagonist polymyxin B. The transition metal chelator deferoxamine did not modify the proinflammatory or cytotoxic responses to the PM10 samples. CONCLUSIONS: The toxicity profile of urban-air PM10 changed with season in a subarctic climate. Particulate-bound endotoxin from soil gram-negative bacteria is suggested as a highly proinflammatory constituent of springtime resuspended road dust.


Assuntos
Poluição do Ar/análise , Desoxiguanosina/análogos & derivados , Estações do Ano , 8-Hidroxi-2'-Desoxiguanosina , Animais , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Dano ao DNA , Desoxiguanosina/biossíntese , Relação Dose-Resposta a Droga , Espectroscopia de Ressonância de Spin Eletrônica , Finlândia , Humanos , Compostos Inorgânicos/análise , Compostos Inorgânicos/toxicidade , Interleucina-6/biossíntese , Macrófagos/citologia , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Camundongos , Óxido Nítrico/biossíntese , Tamanho da Partícula , Hidrocarbonetos Policíclicos Aromáticos/análise , Hidrocarbonetos Policíclicos Aromáticos/toxicidade , Fatores de Tempo , Fator de Necrose Tumoral alfa/biossíntese , Saúde da População Urbana
4.
Toxicol Appl Pharmacol ; 229(2): 146-60, 2008 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-18325559

RESUMO

We investigated the inflammatory and cytotoxic activities of the water-soluble and -insoluble as well as organic-solvent-soluble and -insoluble fractions of urban air fine (PM(2.5-0.2)) and coarse (PM(10-2.5)) particulate samples. The samples were collected with a high volume cascade impactor (HVCI) in 7-week sampling campaigns of selected seasons in six European cities. Mouse macrophage cells (RAW 264.7) were exposed to the samples for 24 h. The production of nitric oxide (NO) and proinflammatory cytokines (TNFalpha, IL-6), and cytotoxicity (MTT-test, apoptosis, cell cycle) were measured. The inflammatory and cytotoxic responses in both size ranges were mostly associated with the insoluble particulate fractions. However, both the water- and organic-solvent-soluble particulate fractions induced TNFalpha production and apoptosis and had some other cytotoxic effects. Soil-derived water-soluble and -insoluble components of the chemical PM(2.5-0.2) mass closure had consistent positive correlations with the responses, while the correlations were negative with the secondary inorganic anions (NO(3)(-), NH(4)(+), non-sea-salt SO(4)(2-)) and particulate organic matter (POM). With the PM(10-2.5) samples, sea salt and soluble soil components correlated positively with the induced toxic responses. In this size range, a possible underestimation of the insoluble, soil-related compounds containing Si and Ca, and biological components of POM, increased uncertainties in the evaluation of associations of the mass closure components with the responses. It is concluded that insoluble components of the complex urban air particulate mixture exert the highest inflammatory and cytotoxic activities in the macrophage cell line but, at the same time, they may operate as carriers for active water- and lipid-soluble components.


Assuntos
Poluentes Atmosféricos/toxicidade , Sobrevivência Celular/efeitos dos fármacos , Inflamação/induzido quimicamente , Macrófagos/efeitos dos fármacos , Animais , Linhagem Celular , Citocinas/biossíntese , Macrófagos/metabolismo , Camundongos , Óxido Nítrico/biossíntese , Tamanho da Partícula , Solubilidade
5.
Toxicol Appl Pharmacol ; 215(3): 341-53, 2006 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-16678872

RESUMO

The impact of long-range transport (LRT) episodes of wildfire smoke on the inflammogenic and cytotoxic activity of urban air particles was investigated in the mouse RAW 264.7 macrophages. The particles were sampled in four size ranges using a modified Harvard high-volume cascade impactor, and the samples were chemically characterized for identification of different emission sources. The particulate mass concentration in the accumulation size range (PM(1-0.2)) was highly increased during two LRT episodes, but the contents of total and genotoxic polycyclic aromatic hydrocarbons (PAH) in collected particulate samples were only 10-25% of those in the seasonal average sample. The ability of coarse (PM(10-2.5)), intermodal size range (PM(2.5-1)), PM(1-0.2) and ultrafine (PM(0.2)) particles to cause cytokine production (TNFalpha, IL-6, MIP-2) reduced along with smaller particle size, but the size range had a much smaller impact on induced nitric oxide (NO) production and cytotoxicity or apoptosis. The aerosol particles collected during LRT episodes had a substantially lower activity in cytokine production than the corresponding particles of the seasonal average period, which is suggested to be due to chemical transformation of the organic fraction during aging. However, the episode events were associated with enhanced inflammogenic and cytotoxic activities per inhaled cubic meter of air due to the greatly increased particulate mass concentration in the accumulation size range, which may have public health implications.


Assuntos
Poluentes Atmosféricos/toxicidade , Incêndios , Macrófagos/efeitos dos fármacos , Fumaça/efeitos adversos , Movimentos do Ar , Poluentes Atmosféricos/análise , Animais , Apoptose/efeitos dos fármacos , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Quimiocina CXCL2 , Quimiocinas/metabolismo , Finlândia , Interleucina-6/metabolismo , Macrófagos/metabolismo , Metais/análise , Camundongos , Nitratos/análise , Óxido Nítrico/biossíntese , Tamanho da Partícula , Hidrocarbonetos Policíclicos Aromáticos/análise , Compostos de Amônio Quaternário/análise , Fumaça/análise , Sulfatos/análise , Fator de Necrose Tumoral alfa/metabolismo
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