Am. J. Respir. Cell Mol. Biol., Vol 17, No. 5, Nov 1997, 642-651.
Airway eosinophils, T cells, Th2-type cytokine mRNA, and hyperreactivity in response to aerosol challenge of allergic mice with previously established pulmonary inflammation
CG Garlisi, A Falcone, JA Hey, TM Paster, X Fernandez, CA Rizzo, M Minnicozzi, H Jones, MM Billah, RW Egan and SP Umland
Allergy and Immunology, Schering-Plough Research Institute, Kenilworth, New Jersey 07033-0539, USA.
Asthma is characterized by acute episodes of nonspecific airway
hyperreactivity and chronic pulmonary inflammation exacerbated by stimuli
including allergen exposure. In order to reproduce the physiologic and
immunologic responses that occur in asthmatic patients, we have
characterized a model of antigen-induced inflammation in which allergic
mice (B6D2F1) that had been challenged once with aerosolized ovalbumin and
had developed a pulmonary cellular infiltrate were rechallenged 1 wk later.
Pulmonary inflammation in rechallenged mice was substantially greater than
that in single-challenged mice. Eosinophils and activated-memory T cells
(CD44+, CD45RBlo) in bronchoalveolar lavage (BAL) fluid accumulated to
higher levels and with faster kinetics in response to the second challenge
than in response to the first challenge. Eosinophils in lung tissue also
accumulated to higher levels but with similar kinetics in response to the
second challenge than in response to the first challenge. Similarly,
interleukin (IL)-4 and IL-5 steady-state mRNA levels in lung tissue
increased after the second challenge and were higher than those measured
after a single challenge. Furthermore, treatment of mice with an anti-IL-5
monoclonal antibody 2 h prior to rechallenge inhibited antigen induced
eosinophil accumulation in the lungs. In mice challenged twice, peak in
vivo bronchoconstrictor responsiveness to acetylcholine was increased
following the second challenge compared with that observed following the
initial challenge. In contrast, ex vivo tracheal smooth muscle contractile
responsiveness to acetylcholine was not altered. Although mucus
accumulation and epithelial damage in pulmonary tissue were evident in mice
challenged twice, these parameters were slightly reduced compared with
those seen at similar times in mice challenged once. Therefore, although
these mice exhibit only slight bronchial epithelial damage, the presence of
significant inflammation and airway hyperreactivity to acetylcholine as
well as slightly increased baseline reactivity demonstrate important
similarities with the pathophysiology of asthma.
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Copyright © 1997 American Thoracic Society.
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