The synergistic interactions of allergic lung inflammation and intratracheal cationic protein.
BACKGROUND
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.


OBJECTIVE
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.


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.
Bates
Jason H T
JH
Vermont Lung Center, Burlington, Vermont, USA. jason.h.bates@uvm.edu
Cojocaru
Ana
A
Haverkamp
Hans C
HC
Rinaldi
Lisa M
LM
Irvin
Charles G
CG
D000818:Animals; D001249:Asthma / Q000139:chemically induced / Q000503:physiopathology*; D016535:Bronchial Hyperreactivity / Q000139:chemically induced / Q000503:physiopathology*; D001985:Bronchial Provocation Tests; D016084:Bronchoconstriction / Q000502:physiology; D016085:Bronchoconstrictor Agents / Q000494:pharmacology*; D004195:Disease Models, Animal; D004357:Drug Synergism; D005260:Female; D051379:Mice; D009130:Muscle, Smooth / Q000503:physiopathology; D010047:Ovalbumin / Q000494:pharmacology*; D011107:Polylysine / Q000494:pharmacology*
D016085:Bronchoconstrictor Agents; D011107:Polylysine; D010047:Ovalbumin