Exposure to ozone induces deleterious responses
in the airways that include shortness of breath,
inflammation, and bronchoconstriction. People
with asthma have increased airway sensitivity to
ozone and other irritants. Dr. Allison Fryer and
colleagues addressed how exposure to ozone affects
the immune and physiological responses in
guinea pigs. Guinea pigs are considered a useful
animal model for studies of respiratory and physiological
responses in humans; their response to
airborne allergens is similar to that in humans and
shares some features of allergic asthma.
Fryer and colleagues had previously observed
that within 24 hours of exposure, ozone not only
induced bronchoconstriction but also stimulated
the production of new cells in the bone marrow,
where all white blood cells develop. As a result
of ozone exposure, increased numbers of newly
synthesized white blood cells, particularly eosinophils,
moved into the blood and lungs.
The central hypothesis of the current study was
that newly synthesized eosinophils recruited to
the lungs 3 days after ozone exposure were beneficial
to the animals because they reduced ozoneinduced
bronchoconstriction. The investigators
also hypothesized that the beneficial effect seen
in normal (nonsensitized) animals was lost in animals
that had been injected with an allergen, ovalbumin
(sensitized). They also planned to explore
the effects of inhibitors of certain cytokines (cellsignaling
molecules).
Immune responses in sensitized animals are
dominated by a Th2 pattern, which is characterized
by the synthesis of cytokines (interleukin
[IL]-4, IL-5, and IL-13) and the Th2 subset of CD4+
T lymphocytes and the cells they activate (predominantly
eosinophils, and B lymphocytes that
switch to making immunoglobulin E [IgE]). Thus,
sensitized animals were used as a model of allergic
humans, whose immune responses tend to be
dominated by IgE.