title: No role for neutrophil elastase in influenza-induced cellular recruitment, cytokine production or airway hyperresponsiveness in mice.
abstract: Previous studies have suggested that in vitro modulation of neutrophil chemokines and inflammatory cytokines by neutrophil elastase (NE) does not translate to the in vivo setting. We aimed to test the role of NE in the recruitment of neutrophils, cytokine production and lung function responses to respiratory viral infection. To address this, we inoculated neutrophil elastase (NE(-/-)) deficient and wild-type (WT) 129Sv mice with 50μL of 10(4.5)pfu Influenza A/Mem71 (H3N1) or a control preparation. Mice were subjected to methacholine (MCh) challenge at 3-4 days post-infection during the peak of cellular inflammation. Inflammation, protein content and cytokines (TNF-α and MIP-2) were assessed in bronchoalveolar lavage fluid. Influenza-infected mice had a heightened responsiveness to MCh, increased cellular inflammation, increased protein leak and altered cytokine production, none of which were influenced by the absence of NE. These data demonstrate that NE does not modulate neutrophil recruitment, cytokine production, epithelial permeability or responsiveness to bronchoconstricting agents during acute influenza infection in mice.
authors.affiliation: Telethon Institute for Child Health Research, Subiaco, Western Australia, Australia.
authors.forename: Rachel E
authors.initials: RE
authors.lastname: Foong
authors.forename: Peter D
authors.initials: PD
authors.lastname: Sly
authors.forename: Alexander N
authors.initials: AN
authors.lastname: Larcombe
authors.forename: Graeme R
authors.initials: GR
authors.lastname: Zosky
mesh_terms: D000403:Airway Resistance / Q000187:drug effects / Q000235:genetics; D000818:Animals; D016535:Bronchial Hyperreactivity / Q000209:etiology* / Q000235:genetics / Q000276:immunology*; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology / Q000276:immunology; D016085:Bronchoconstrictor Agents / Q000008:administration & dosage; D054426:Chemokine CXCL2 / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005786:Gene Expression Regulation / Q000187:drug effects; D019272:Leukocyte Elastase / Q000172:deficiency / Q000378:metabolism*; D008168:Lung / Q000187:drug effects / Q000503:physiopathology* / Q000821:virology; D016210:Methacholine Chloride / Q000008:administration & dosage; D051379:Mice; D018345:Mice, Knockout; D009976:Orthomyxoviridae Infections / Q000150:complications* / Q000235:genetics; D018709:Statistics, Nonparametric; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D016085:Bronchoconstrictor Agents; D054426:Chemokine CXCL2; C404915:Cxcl2 protein, mouse; D016207:Cytokines; D014409:Tumor Necrosis Factor-alpha; D016210:Methacholine Chloride; D019272:Leukocyte Elastase