The Synergistic Interactions of Allergic Lung Inflammation and Intratracheal Cationic Protein
- 1 February 2008
- journal article
- research article
- Published by American Thoracic Society in American Journal of Respiratory and Critical Care Medicine
- Vol. 177 (3), 261-268
- https://doi.org/10.1164/rccm.200706-832oc
Abstract
Rationale: Airways hyperresponsiveness (AHR) is a hallmark feature of asthma, and can be caused by various disparate mechanisms. Mouse models of AHR have been useful for studying these mechanisms in isolation, but such models still typically do not exhibit the same degree of AHR as seen in severe human asthma. We hypothesized that more severe AHR in mice could be achieved by imbuing them with more than one mechanism of AHR. Objectives: We sought to determine if the airway wall thickening accompanying allergic inflammation and the exaggerated smooth muscle shortening induced by intratracheal cationic protein could act together to produce a severe form of AHR. Methods: We used the forced oscillation technique to measure methacholine responsiveness in BALB/c mice that had been sensitized and challenged with ovalbumin followed by an intratracheal instillation of poly-l-lysine. Measurements and Main Results: We found that both ovalbumin and poly-l-lysine treatment alone caused moderate levels of AHR. When the two treatments were combined, however, they synergized in terms of their effect on lung stiffness to an extent that could even be fatal, reflecting a significantly enhanced level of airway closure. Conclusions: Our results suggest that mechanistic synergy between airway wall thickening and exaggerated smooth muscle shortening produces a more germane mouse model of asthma that may have particular relevance to the pathophysiology of the acute severe asthma exacerbation.Keywords
This publication has 53 references indexed in Scilit:
- Airway Hyperresponsiveness in Allergically Inflamed MiceAmerican Journal of Respiratory and Critical Care Medicine, 2007
- Asthma Control during the Year after Bronchial ThermoplastyNew England Journal of Medicine, 2007
- Airway Smooth Muscle as a Target for Asthma TherapyNew England Journal of Medicine, 2007
- The Estimation of Lung Mechanics Parameters in the Presence of Pathology: A Theoretical AnalysisAnnals of Biomedical Engineering, 2006
- Airway hyperresponsiveness induced by cationic proteins in vivo: site of actionAmerican Journal of Physiology-Lung Cellular and Molecular Physiology, 2005
- Systems Biology: A Brief OverviewScience, 2002
- New insights from lung functionCurrent Opinion in Allergy and Clinical Immunology, 2001
- New insights from lung functionCurrent Opinion in Allergy and Clinical Immunology, 2001
- An equivalent network for resistance and temperature coefficient of resistance versus temperature and composition of thick resistive filmsJournal of Applied Physics, 1987
- Anticholinergic Drugs and AsthmaSeminars in Respiratory and Critical Care Medicine, 1987