Exaggerated airway narrowing in mice treated with intratracheal cationic protein.
Airway hyperresponsiveness in mice with allergic airway inflammation can be attributed entirely to exaggerated closure of peripheral airways (Wagers S, Lundblad LK, Ekman M, Irvin CG, and Bates JHT. J Appl Physiol 96: 2019-2027, 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 submaximal 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 that we found previously in mice with allergically inflamed lungs.
Bates
Jason H T
JH
Vermont Lung Center, University of Vermont College of Medicine, Burlington, VT 05405-0075, USA. jason.h.bates@uvm.edu
Wagers
Scott S
SS
Norton
Ryan J
RJ
Rinaldi
Lisa M
LM
Irvin
Charles G
CG
D000280:Administration, Inhalation; D000818:Animals; D016535:Bronchial Hyperreactivity / Q000139:chemically induced* / Q000503:physiopathology; D016084:Bronchoconstriction; D016085:Bronchoconstrictor Agents / Q000008:administration & dosage / Q000494:pharmacology; D002412:Cations; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D007442:Intubation, Intratracheal; D016210:Methacholine Chloride / Q000008:administration & dosage / Q000494:pharmacology; D051379:Mice; D008807:Mice, Inbred BALB C; D009130:Muscle, Smooth / Q000187:drug effects / Q000503:physiopathology; D011107:Polylysine / Q000008:administration & dosage; D011506:Proteins / Q000008:administration & dosage*; D020545:Respiratory Mucosa / Q000187:drug effects; D012137:Respiratory System / Q000187:drug effects / Q000503:physiopathology; D013997:Time Factors
D016085:Bronchoconstrictor Agents; D002412:Cations; D011506:Proteins; D016210:Methacholine Chloride; D011107:Polylysine