title: Effects of environmental aerosols on airway hyperresponsiveness in a murine model of asthma.
abstract: Increased morbidity in persons suffering from inflammatory lung diseases, such as asthma and bronchitis, has been associated with air pollution particles. One hypothesis is that particles can cause an amplification of the pulmonary inflammation associated with these diseases, thus worsening affected individuals' symptoms. This hypothesis was tested in a murine model of asthma by inhalation exposure to (1) concentrated air particles (CAPs), (2) the leachate of residual oil fly ash (ROFA-S), and (3) lipopolysaccharide (LPS). Allergen-sensitized mice (ip ovalbumin, OVA) were 21 days old when challenged with an aerosol of 3% OVA in phosphate-buffered saline (PBS) for 10 min (controls were challenged with PBS only) for 3 days. On the same days, mice were further exposed to 1 of 3 additional agents: CAPs (or filtered air) for 6 h/day; LPS (5 microg/ml, or PBS) for 10 min/day; or ROFA-S (leachate of 50 mg/ml, or PBS) for 30 min on day 2 only. At 24 h later, mice challenged with OVA aerosol showed airway inflammation and airway hyperresponsiveness (AHR) to methacholine (Mch), features absent in mice challenged with PBS alone. Both OVA- and PBS-challenged mice subsequently exposed to ROFA-S showed increased AHR to Mch when compared to their respective controls (OVA only or PBS only). In contrast, when OVA-challenged mice were further exposed to CAPs or LPS, no changes in AHR were seen in comparison to mice challenged with OVA only. Bronchoalveolar lavage (BAL) analysis and histopathology 48 h postexposure showed OVA-induced allergic inflammation. No significant additional effects were caused by CAPs or ROFA-S. LPS, in contrast, caused significant increases in total cell, macrophage, and polymorphonuclear cell numbers. The data highlight discordance between airway inflammation and hyperresponsiveness.
authors.affiliation: Harvard School of Public Health, Bldg. II-221, 665 Huntington Ave, Boston, MA 02115, USA.
authors.forename: C A
authors.initials: CA
authors.lastname: Goldsmith
authors.forename: K
authors.initials: K
authors.lastname: Hamada
authors.forename: Y
authors.initials: Y
authors.lastname: Ning
authors.forename: G
authors.initials: G
authors.lastname: Qin
authors.forename: P
authors.initials: P
authors.lastname: Catalano
authors.forename: G G
authors.initials: GG
authors.lastname: Krishna Murthy
authors.forename: J
authors.initials: J
authors.lastname: Lawrence
authors.forename: L
authors.initials: L
authors.lastname: Kobzik
mesh_terms: D000393:Air Pollutants / Q000009:adverse effects*; D000485:Allergens / Q000633:toxicity; D000818:Animals; D001249:Asthma / Q000473:pathology / Q000503:physiopathology*; D001273:Atmosphere Exposure Chambers; D016535:Bronchial Hyperreactivity / Q000473:pathology / Q000503:physiopathology*; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D002244:Carbon / Q000633:toxicity; D002452:Cell Count; D003031:Coal / Q000633:toxicity; D060729:Coal Ash; D004195:Disease Models, Animal; D004804:Eosinophils / Q000378:metabolism; D007073:Immunoglobulin E / Q000032:analysis; D019570:Inhalation Exposure / Q000009:adverse effects*; D008070:Lipopolysaccharides / Q000633:toxicity; D051379:Mice; D008807:Mice, Inbred BALB C; D010047:Ovalbumin / Q000276:immunology; D052638:Particulate Matter; D010993:Plethysmography, Whole Body; D012129:Respiratory Function Tests
chemical_list: D000393:Air Pollutants; D000485:Allergens; D003031:Coal; D060729:Coal Ash; D008070:Lipopolysaccharides; D052638:Particulate Matter; D007073:Immunoglobulin E; D002244:Carbon; D010047:Ovalbumin