Development of a novel guinea pig model of allergic airways disease
Development of a novel guinea pig model of allergic airways disease
Throughout this thesis the development and characterisation of a guinea pig model of allergic disease is described. These studies were based on an existing model which presented changes in bronchoalveolar lavage (BAL) cellular contents, lung histology and lung mechanics, indicative of an allergen-induced airway response. However, these changes were found to be variable in magnitude or even absent. Since guinea-pigs are obligate nose breathers, the amount of aerosol deposited in the upper and lower airways was investigated. The majority of the radiolabelled aerosol was found to be deposited within the nasal region, suggesting a low degree of sensitisation reponsible for the variability in the response to allergen.
A method for bypassing the nose by temporary endotracheal intubation was devised. Radio-aerosol distribution in these guinea pigs showed mainly lung deposition. This allowed sensitisation and challenge of guinea pigs directly to the lungs without the use of surgical procedures. Allergen sensitisation by this route resulted in high numbers of neutrophils and eosinophils in bone marrow, and an eosinophilia in BAL associated with an increase in major basic protein (MBP) levels, suggesting activation of these cells. Following allergen challenge pulmonary function, leucocyte influx into the lung and mediator levels in BAL were investigated. Respiratory parameters were measured in conscious guinea pigs by whole body plethysmography. Allergen challenge resulted in an early reaction which was evident at 15 minutes with an increase in airways resistance and a decrease in specific airways conductance. Levels had returned to pre-challenge baseline by 2 hours. Despite greater magnitude changes than nasally sensitised guinea pigs, no later phase response was evident. These changes were associated with an early neutrophilia which peaked at 6 hours in both BAL and lung tissue. This was followed by a slower influx of eosinophils into BAL which started at 24 hours and reached its maximum at 72 hours.
University of Southampton
Seminario, María Cristina
1993
Seminario, María Cristina
Seminario, María Cristina
(1993)
Development of a novel guinea pig model of allergic airways disease.
University of Southampton, Doctoral Thesis.
Record type:
Thesis
(Doctoral)
Abstract
Throughout this thesis the development and characterisation of a guinea pig model of allergic disease is described. These studies were based on an existing model which presented changes in bronchoalveolar lavage (BAL) cellular contents, lung histology and lung mechanics, indicative of an allergen-induced airway response. However, these changes were found to be variable in magnitude or even absent. Since guinea-pigs are obligate nose breathers, the amount of aerosol deposited in the upper and lower airways was investigated. The majority of the radiolabelled aerosol was found to be deposited within the nasal region, suggesting a low degree of sensitisation reponsible for the variability in the response to allergen.
A method for bypassing the nose by temporary endotracheal intubation was devised. Radio-aerosol distribution in these guinea pigs showed mainly lung deposition. This allowed sensitisation and challenge of guinea pigs directly to the lungs without the use of surgical procedures. Allergen sensitisation by this route resulted in high numbers of neutrophils and eosinophils in bone marrow, and an eosinophilia in BAL associated with an increase in major basic protein (MBP) levels, suggesting activation of these cells. Following allergen challenge pulmonary function, leucocyte influx into the lung and mediator levels in BAL were investigated. Respiratory parameters were measured in conscious guinea pigs by whole body plethysmography. Allergen challenge resulted in an early reaction which was evident at 15 minutes with an increase in airways resistance and a decrease in specific airways conductance. Levels had returned to pre-challenge baseline by 2 hours. Despite greater magnitude changes than nasally sensitised guinea pigs, no later phase response was evident. These changes were associated with an early neutrophilia which peaked at 6 hours in both BAL and lung tissue. This was followed by a slower influx of eosinophils into BAL which started at 24 hours and reached its maximum at 72 hours.
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Published date: 1993
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Local EPrints ID: 462370
URI: http://eprints.soton.ac.uk/id/eprint/462370
PURE UUID: e730cc29-e4b2-4632-af32-ef7c8b2187e6
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Date deposited: 04 Jul 2022 19:06
Last modified: 04 Jul 2022 19:06
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Author:
María Cristina Seminario
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