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J Appl Physiol (October 20, 2005). doi:10.1152/japplphysiol.01013.2005
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Submitted on August 22, 2005
Accepted on October 17, 2005

EXAGGERATED AIRWAY NARROWING IN MICE TREATED WITH INTRA-TRACHEAL CATIONIC PROTEIN

Jason H.T. Bates1*, Scott S. Wagers1, Ryan J. Norton1, Lisa M. Rinaldi1, and Charles G. Irvin1

1 Department of Medicine, University of Vermont College of Medicine, Burlington, Vermont, USA

* To whom correspondence should be addressed. E-mail: jason.h.bates{at}uvm.edu.

Airway hyperresponsiveness in mice with allergic airway inflammation can be attributed entirely to exaggerated closure of peripheral airways (J Appl Physiol 96: 2019-27, 2004). However, clinical asthma can be characterized by hyperresponsiveness of the central airways as well as the lung periphery. We therefore sought to establish a complementary model of hyperresponsiveness in the mouse due to excessive narrowing of the airways. We treated mice with a tracheal instillation of the cationic protein poly-L-lysine (PLL), hypothesizing that this would reduce the barrier function of the epithelium and thereby render the underlying airway smooth muscle more accessible to aerosolized methacholine. The PLL-treated animals were hypersensitive to methacholine: they exhibited an exaggerated response to sub-maximal doses but had a maximal response that was similar to controls. With the aid of a computational model of the mouse lung we conclude that the methacholine responsiveness of PLL-treated mice is fundamentally different in nature to the hyperresponsiveness we found previously in mice with allergically inflamed lungs.




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