title: Acute effects of inhaled urban particles and ozone: lung morphology, macrophage activity, and plasma endothelin-1.
abstract: 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 microm; 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.
authors.affiliation: Environmental and Occupational Toxicology Division, Environmental Health Directorate, Health Canada, Ottawa, Ontario.
authors.forename: L
authors.initials: L
authors.lastname: Bouthillier
authors.forename: R
authors.initials: R
authors.lastname: Vincent
authors.forename: P
authors.initials: P
authors.lastname: Goegan
authors.forename: I Y
authors.initials: IY
authors.lastname: Adamson
authors.forename: S
authors.initials: S
authors.lastname: Bjarnason
authors.forename: M
authors.initials: M
authors.lastname: Stewart
authors.forename: J
authors.initials: J
authors.lastname: Guénette
authors.forename: M
authors.initials: M
authors.lastname: Potvin
authors.forename: P
authors.initials: P
authors.lastname: Kumarathasan
mesh_terms: D000818:Animals; D001685:Biological Factors / Q000378:metabolism; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry / Q000166:cytology; D002470:Cell Survival / Q000187:drug effects; D002947:Cities; D004391:Dust / Q000009:adverse effects*; D019332:Endothelin-1 / Q000097:blood; D008168:Lung / Q000276:immunology / Q000473:pathology* / Q000648:ultrastructure; D008264:Macrophages / Q000166:cytology / Q000378:metabolism; D008297:Male; D010126:Ozone / Q000276:immunology*; D011506:Proteins / Q000032:analysis; D051381:Rats; D011916:Rats, Inbred F344; D013047:Specific Pathogen-Free Organisms
chemical_list: D001685:Biological Factors; D004391:Dust; D019332:Endothelin-1; D011506:Proteins; D010126:Ozone