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
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.