File(s) under permanent embargo
No role for neutrophil serine proteases in influenza-induced hyperresponsiveness
Background: It is well established that acute influenza (flu) infection results in airway hyperresponsiveness (AHR) and infiltration of neutrophils to the airway. Despite this, the mechanisms of AHR are poorly understood or studied. We have previously shown that flu-induced AHR results from increased epithelial permeability. Given that neutrophil recruitment has been found to be involved in increased epithelial permeability we investigated the potential role of the neutrophil products, neutrophil serine proteases (NSPs), including neutrophil elastase (NE) and cathepsin G, (CG) in flu-induced.
Methods: We infected wild-type 129Sv mice and 129Sv mice deficient in NE, CG and both NE and CG with 104.5 pfu flu (A/Memphis/1/71 H3N2) or a mock infected cell preparation as controls. AHR to methacholine (MCh) challenge was assessed using a modification of the forced oscillation technique during the acute phase of infection. Following this, bronchoalveolar lavage (BAL) samples were collected and lung tissue homogenized. BALs were used to ascertain total cell counts (TCC) and differential cell counts (macrophages, neutrophils, eosinophils and lymphocytes) under light microscopy and homogenized lungs were used for viral titre assays.
Results: Flu-infected mice were significantly more responsive to MCh, compared to genotype-matched controls (p < 0.001) however the magnitude of this effect was not modified by genotype (p = 0.63). Similarly, cellular inflammation was significantly increased in fluinfected mice (p < 0.001) but again there was no effect of genotype (p = 0.92). Viral titre assays showed that the virus had replicated in the lungs, confirming infection in each of the four genotypes.
Conclusion: NSPs do not appear to be responsible for the flu-induced AHR that results from increased epithelial permeability.
History
Publication title
RespirologyVolume
15 (Suppl. 1)Editors
P BardinPagination
A49ISSN
1323-7799Department/School
Tasmanian School of MedicinePublisher
Wiley-Blackwell Publishing AsiaPlace of publication
AustraliaEvent title
The Thoracic Society of Australia & New Zealand Annual Scientific Meeting 2010Event Venue
Brisbane, AustraliaDate of Event (Start Date)
2010-03-20Date of Event (End Date)
2010-03-24Repository Status
- Restricted