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Articles in PresS, published online ahead of print March 22, 2002
Am J Physiol Lung Cell Mol Physiol, 10.1152/ajplung.00324.2001
Submitted on August 13, 2001
Accepted on February 24, 2002
1 Pediatrics, Medicine, University of Utah, Salt Lake City, UT, USA
* To whom correspondence should be addressed. E-mail: kurt.albertine{at}hsc.utah.edu.
Airway hyperresponsiveness, airway inflammation and reversible airway obstruction are physiologic hallmarks of asthma. These responses are increasingly being studied in murine models of antigen exposure and challenge, using whole-body plethysmography to non-invasively assess airway hyperresponsiveness. This approach infrequently has been correlated with indices of airway hyperresponsiveness measured by invasive means. Furthermore, correlation with quantitative histologic data for tissue infiltration by inflammatory and immune cells, particularly in the wall of airways, during daily airway challenge is lacking. To address these uncertainties, we used C57BL/6 mice that were immunized with ovalbumin, or vehicle (saline), and sensitized to aerosolized ovalbumin or vehicle 8 days later. The mice were subsequently exposed to aerosolized ovalbumin or vehicle, respectively, on days 14-22. We assessed airway hyperresponsiveness to methacholine non-invasively on days 14, 15, 18 or 22; we studied the same mice 24 hours later while they were anesthetized for invasive analyses of airway hyperresponsiveness. Plasma total IgE concentration was significantly higher in the ovalbumin-treated mice compared to the vehicle-treated mice, but this did not correlate with eosinophil number. Peak airway hyperresponsiveness measured by either approach correlated early during daily antigen challenge (days 14 and 15), but this correlation was lost later during subsequent daily antigen challenges (days 18 and 22). On days 14 and 15, peak airway hyperresponsiveness correlated with transmigration of neutrophils and macrophages, but not lymphocytes, into the peribronchovascular connective tissue sheaths. This extravascular accumulation was found to be focal by 3-dimensional microscopy. We conclude that while ovalbumin treatment changed lung function in mice, correlation between non-invasive and invasive measures of peak airway hyperresponsiveness was inconsistent.
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