We studied acute responses of rat lungs to inhalation of urban particulate matter and ozone. Exposure to particles (40 mg/m3 for 4 hours; mass median aerodynamic diameter, 4 to 5 μm; Ottawa urban dust, EHC-93), followed by 20 hours in clean air, did not result in acute lung injury. Nevertheless, inhalation of particles resulted in decreased production of nitric oxide (nitrite) and elevated secretion of macrophage inflammatory protein-2 from lung lavage cells. Inhalation of ozone (0.8 parts per million for 4 hours) resulted in increased neutrophils and protein in lung lavage fluid. Ozone alone also decreased phagocytosis and nitric oxide production and stimulated endothelin-1 secretion by lung lavage cells but did not modify secretion of macrophage inflammatory protein-2. Co-exposure to particles potentiated the ozone-induced septal cellularity in the central acinus but without measurable exacerbation of the ozone-related alveolar neutrophilia and permeability to protein detected by lung lavage. The enhanced septal thickening was associated with elevated production of both macrophage inflammatory protein-2 and endothelin-1 by lung lavage cells. Interestingly, inhalation of urban particulate matter increased the plasma levels of endothelin-1, but this response was not influenced by the synergistic effects of ozone and particles on centriacinar septal tissue changes. This suggests an impact of the distally distributed particulate dose on capillary endothelial production or filtration of the vasoconstrictor. Overall, equivalent patterns of effects were observed after a single exposure or three consecutive daily exposures to the pollutants. The experimental data are consistent with epidemiological evidence for acute pulmonary effects of ozone and respirable particulate matter and suggest a possible mechanism whereby cardiovascular effects may be induced by particle exposure. In a broad sense, acute biological effects of respirable particulate matter from ambient air appear related to paracrine/endocrine disruption mechanisms. We studied acute responses of rat lungs to inhalation of urban particulate matter and ozone. Exposure to particles (40 mg/m3 for 4 hours; mass median aerodynamic diameter, 4 to 5 μm; Ottawa urban dust, EHC-93), followed by 20 hours in clean air, did not result in acute lung injury. Nevertheless, inhalation of particles resulted in decreased production of nitric oxide (nitrite) and elevated secretion of macrophage inflammatory protein-2 from lung lavage cells. Inhalation of ozone (0.8 parts per million for 4 hours) resulted in increased neutrophils and protein in lung lavage fluid. Ozone alone also decreased phagocytosis and nitric oxide production and stimulated endothelin-1 secretion by lung lavage cells but did not modify secretion of macrophage inflammatory protein-2. Co-exposure to particles potentiated the ozone-induced septal cellularity in the central acinus but without measurable exacerbation of the ozone-related alveolar neutrophilia and permeability to protein detected by lung lavage. The enhanced septal thickening was associated with elevated production of both macrophage inflammatory protein-2 and endothelin-1 by lung lavage cells. Interestingly, inhalation of urban particulate matter increased the plasma levels of endothelin-1, but this response was not influenced by the synergistic effects of ozone and particles on centriacinar septal tissue changes. This suggests an impact of the distally distributed particulate dose on capillary endothelial production or filtration of the vasoconstrictor. Overall, equivalent patterns of effects were observed after a single exposure or three consecutive daily exposures to the pollutants. The experimental data are consistent with epidemiological evidence for acute pulmonary effects of ozone and respirable particulate matter and suggest a possible mechanism whereby cardiovascular effects may be induced by particle exposure. In a broad sense, acute biological effects of respirable particulate matter from ambient air appear related to paracrine/endocrine disruption mechanisms. Human health impacts of air pollution have been recognized for over a century. In recent years, episodic variations of respirable particles of less than a hundred micrograms per cubic meter have been associated with increases, on following days, of respiratory and cardiovascular morbidity and mortality.1Bates DV Sizto R Relationships between air pollution levels and hospital admissions in Southern Ontario.Can J Public Health. 1983; 74: 117-122PubMed Google Scholar, 2Dockery DW Pope CA Xu X Spengler JD Ware JH Fay ME Ferris BG Speizer FE An association between air pollution and mortality in six U.S. cities.N Engl J Med. 1993; 329: 1753-1759Crossref PubMed Scopus (6269) Google Scholar, 3Burnett RT Dales RE Raizenne ME Krewski D Summers PW Roberts GR Raad-Young M Dann T Brook J Effects of low ambient levels of ozone and sulfates on the frequency of respiratory admissions to Ontario hospitals.Environ Res. 1994; 65: 172-194Crossref PubMed Scopus (239) Google Scholar, 4Burnett RT Dales RE Krewski D Vincent R Dann T Brook JR Associations between ambient particulate sulfate and admissions to Ontario hospitals for cardiac and respiratory diseases.Am J Epidemiol. 1995; 142: 15-22PubMed Google The between epidemiological for a but the of acute health effects to low levels to and of a biological for a association the of biological effects of respirable particles and of with the of a of data on the in biological effects of particulate matter from ambient air, for experimental inhalation of inhalation exposure of to urban particulate matter may not acute in the lung particles centriacinar induced by R J M pulmonary of urban particulate matter and J Google by particles the of a of and J J J R inflammatory and by rat alveolar and cells and in rat lung after J 1993; PubMed Scopus Google Scholar, J J macrophage and production in a rat of pulmonary and Health. 1995; PubMed Scopus Google This to the of macrophage followed by of and and a of to may be to of inflammatory by particles in In urban particles are not but by of the of D Vincent R Brook J of ambient air particles to rat lung of and In PubMed Scopus Google or by the of a response in R Brook JR RT of in cells by of particles from ambient PubMed Scopus Google This suggests a to biological effects of be or in in macrophage by PubMed Scopus Google Scholar, of ambient air related to lung PubMed Scopus Google responses be to of in with lung of in by of urban been than a J particles and pulmonary in and in effects of ambient air and Res. PubMed Scopus Google low of respirable particles are associated with acute cardiac in to associated with pulmonary RT Dales RE Krewski D Vincent R Dann T Brook JR Associations between ambient particulate sulfate and admissions to Ontario hospitals for cardiac and respiratory diseases.Am J Epidemiol. 1995; 142: 15-22PubMed Google Ozone been associated with pulmonary effects but not with cardiac morbidity and this may not be be on the of in between particles and RT Dales RE Krewski D Vincent R Dann T Brook JR Associations between ambient particulate sulfate and admissions to Ontario hospitals for cardiac and respiratory diseases.Am J Epidemiol. 1995; 142: 15-22PubMed Google Ozone in the respiratory and the of alveolar the the alveolar from particles the capillary in a The lung the levels of a of cardiovascular a not by endothelial cells of the lung but also by and pulmonary cells. levels of have been in a of and acute lung JR and the J Med. 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We a in the of with with respiratory or cardiovascular of the in the health of increased daily of hospital DV Sizto R Relationships between air pollution levels and hospital admissions in Southern Ontario.Can J Public Health. 1983; 74: 117-122PubMed Google Scholar, 3Burnett RT Dales RE Raizenne ME Krewski D Summers PW Roberts GR Raad-Young M Dann T Brook J Effects of low ambient levels of ozone and sulfates on the frequency of respiratory admissions to Ontario hospitals.Environ Res. 1994; 65: 172-194Crossref PubMed Scopus (239) Google Scholar, 4Burnett RT Dales RE Krewski D Vincent R Dann T Brook JR Associations between ambient particulate sulfate and admissions to Ontario hospitals for cardiac and respiratory diseases.Am J Epidemiol. 1995; 142: 15-22PubMed Google DW Pope CA Xu X Spengler JD Ware JH Fay ME Ferris BG Speizer FE An association between air pollution and mortality in six U.S. cities.N Engl J Med. 1993; 329: 1753-1759Crossref PubMed Scopus (6269) Google We are to and for with the and to for and
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