Effects of environmental aerosols on airway hyperresponsiveness in a murine model of asthma

Citation
Caw. Goldsmith et al., Effects of environmental aerosols on airway hyperresponsiveness in a murine model of asthma, INHAL TOXIC, 11(11), 1999, pp. 981-998
Citations number
28
Categorie Soggetti
Pharmacology & Toxicology
Journal title
INHALATION TOXICOLOGY
ISSN journal
08958378 → ACNP
Volume
11
Issue
11
Year of publication
1999
Pages
981 - 998
Database
ISI
SICI code
0895-8378(199911)11:11<981:EOEAOA>2.0.ZU;2-W
Abstract
Increased morbidity in persons suffering from inflammatory lung diseases, s uch as asthma and bronchitis, has been associated with air pollution partic les. One hypothesis is that particles can cause an amplification of the pul monary inflammation associated with these diseases, thus worsening affected individuals' symptoms. This hypothesis was tested in a murine model of ast hma by inhalation exposure to (1) concentrated air particles (CAPs), (2) th e leachate of residual oil fly ash (ROFA-S), and (3) lipopolysaccharide (LP S). Allergen-sensitized mice (ip ovalbumin, OVA) were 21 days old when chal lenged 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 ai r) for 6 h/day; LPS (5 mu g/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 challen ged with OVA aerosol showed airway inflammation and airway hyperresponsiven ess (AHR) to methacholine (Mch), features absent in mice challenged with PB S alone. Both OVA- and PBS-challenged mice subsequently exposed to ROFA-S s howed increased AHR to Mch when compared to their respective controls (OVA only or PBS only). In contrast, when OVA-challenged mice were further expos ed to CAPs or LPS, no changes in AHR were seen in comparison to mice challe nged with OVA only. Bronchoalveolar lavage (BAL) analysis and histopatholog y 48 h postexposure showed OVA-induced allergic inflammation. No significan t additional effects were caused by CAPs or ROFA-S. LPS, in contrast, cause d significant increases in total cell, macrophage, and polymorphonuclear ce ll numbers. The data highlight discordance between airway inflammation and hyperresponsiveness.