title: Exaggerated airway narrowing in mice treated with intratracheal cationic protein.
abstract: 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.
authors.affiliation: Vermont Lung Center, University of Vermont College of Medicine, Burlington, VT 05405-0075, USA. jason.h.bates@uvm.edu
authors.forename: Jason H T
authors.initials: JH
authors.lastname: Bates
authors.forename: Scott S
authors.initials: SS
authors.lastname: Wagers
authors.forename: Ryan J
authors.initials: RJ
authors.lastname: Norton
authors.forename: Lisa M
authors.initials: LM
authors.lastname: Rinaldi
authors.forename: Charles G
authors.initials: CG
authors.lastname: Irvin
mesh_terms: 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
chemical_list: D016085:Bronchoconstrictor Agents; D002412:Cations; D011506:Proteins; D016210:Methacholine Chloride; D011107:Polylysine