Re-exposure to Ova, generally by the inhaled route then triggers

Re-exposure to Ova, generally by the inhaled route then triggers the effector phase (Chang, Gong, Chen, & Mak, 2011). Lung function can be measured in conscious, spontaneously breathing animals using whole body plethysmography which allows for assessment of multiple functional responses in the same animal over several days. Mice are the most commonly used species for modelling aspects of asthma, especially inflammation. Guinea-pigs are no longer used as widely but represent valuable models, especially for functional parameters such as the EAR and LAR (reviewed in Canning & Chou, 2008). Guinea-pigs have a similar distribution of mast cells, to humans (Fuchs et al., 2012). Also, the EAR bronchoconstriction

is pronounced and mediated check details by histamine, cysteinyl leukotrienes and prostaglandins in both species, contrasting with mice where the EAR bronchoconstriction is minimal and mediated by 5-HT (Fernandez-Rodriguez et al., 2008, Moffatt et al., 2004, Ressmeyer et al., 2006 and Zosky et al., 2008). Several groups have demonstrated isolated characteristics of asthma such as AHR, EAR and LAR in guinea-pigs (Riley et al., 2013 and Suda et al., 2009). However, most studies do not assess all of these characteristics in the same model together with inflammatory cell recruitment, which has potential limitations for using them to assess drug efficacy of novel treatments (Stevenson & Birrell,

2011). Within this laboratory, a model demonstrating an EAR, LAR, AHR and airway inflammation to Ova challenge in guinea-pigs has been developed (Evans

et al., 2012). However, this model has required optimisation Carnitine palmitoyltransferase II on several occasions learn more over the years to continue to produce these features. Lewis, Johnson, and Broadley (1996) modified the allergen challenge conditions to stop the need for mepyramine, which prevents fatal anaphylaxis. Smith and Broadley (2007) modified the sensitisation conditions because of the loss of key features over time. They increased the amount of Ova used and the number of injections given. This restored the EAR, LAR and AHR to Ova challenge. Five years later, at the beginning of the present study the responses had again waned with a loss of the LAR and AHR. The aim of this study was to re-establish an acute guinea-pig model of asthma displaying early and late asthmatic responses, airway hyperresponsiveness and airway inflammation as demonstrated by Smith and Broadley (2007) and Evans et al. (2012). All chemicals were obtained from Sigma-Aldrich, UK or Fisher-Scientific, UK unless stated otherwise. Male Dunkin-Hartley guinea-pigs, 200–300 g were purchased from Harlan Ltd, UK or Charles River, Germany. Guinea-pigs were housed in pathogen free conditions with 12 h light/dark cycles. All procedures were carried out in accordance with Home office license conditions of the Animals (Scientific Procedures) Act 1986 covering animal husbandry and severity limits and EU Directive 2010/63/EU for animal experiments.

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