Foong, RE and Larcombe, AN and Zosky, GR and Sly, PD, No role for neutrophil serine proteases in influenza-induced hyperresponsiveness, Respirology, 20-24 March 2010, Brisbane, Australia, pp. A49. ISSN 1323-7799 (2010) [Conference Extract]
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.
|Item Type:||Conference Extract|
|Research Division:||Medical and Health Sciences|
|Research Group:||Cardiorespiratory Medicine and Haematology|
|Research Field:||Respiratory Diseases|
|Objective Group:||Clinical Health (Organs, Diseases and Abnormal Conditions)|
|Objective Field:||Respiratory System and Diseases (incl. Asthma)|
|Author:||Zosky, GR (Associate Professor Graeme Zosky)|
|Deposited By:||Medicine (Discipline)|
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