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Spleen tyrosine kinase (Syk) plays a critical role in regulation of immune and inflammatory responses. This thesis investigated the role of Syk in the development of the asthma phenotype in acute and chronic mouse models of allergic airways inflammation. Airway hyperresponsiveness (AHR) to methacholine and inflammation increased significantly in HDM-induced compared with the saline control mice. We demonstrated that in vivo inhibition of Syk by selective Syk inhibitors, and genetic deletion of Syk using conditional Syk knockout mice attenuated AHR despite of inflammatory cell influx in the lung. Histological analysis showed airway remodeling in the chronic model, which was attenuated to some degree by deletion of Syk. This study identified a role of Syk in airway hyperresponsiveness and remodeling without significantly affecting leukocyte recruitment in HDM model of airways disease. My results support the improvement of therapeutic strategies in asthma by targeting the Syk pathway.

Spleen tyrosine kinase (Syk) plays a critical role in regulation of immune and inflammatory responses. This thesis investigated the role of Syk in the development of the asthma phenotype in acute and chronic mouse models of allergic airways inflammation. Airway hyperresponsiveness (AHR) to methacholine and inflammation increased significantly in HDM-induced compared with the saline control mice. We demonstrated that in vivo inhibition of Syk by selective Syk inhibitors, and genetic deletion of Syk using conditional Syk knockout mice attenuated AHR despite of inflammatory cell influx in the lung. Histological analysis showed airway remodeling in the chronic model, which was attenuated to some degree by deletion of Syk. This study identified a role of Syk in airway hyperresponsiveness and remodeling without significantly affecting leukocyte recruitment in HDM model of airways disease. My results support the improvement of therapeutic strategies in asthma by targeting the Syk pathway.

β-(1,3)-Glucan is present in mould cell walls and frequently detected in house dust mite (HDM) faeces. β-Glucan exposure is thought to be associated with pulmonary allergic inflammation in mouse and man, although the published data are inconsistent. Here, we show that highly purified β-glucan exacerbates HDM-induced eosinophilic, T helper 2 type airway responses by acting as an adjuvant, promoting activation, proliferation and polarisation of HDM-specific T cells (1-Derβ T cells). We therefore provide definitive evidence that β-glucan can influence allergic pulmonary inflammation.

The United States Environmental Protection Agency acknowledges that indoor environments can impact the health of students and can affect concentration, attendance, and student performance (USEPA 2008). In a school year, children are required by the Florida Department of Education to be in school for a total of 180 days, which is 795 hours spent in a classroom (FLDOE 2008). In the elementary school setting, kindergarten classes typically spend a portion of the school day with floor-based activities. The American Lung Association (ALA) states that over 6.8 million children under the age of 18 are affected by asthma (ALA 2008). Allergic reactions and/or sensitization to allergens such as dust, animal dander, and cockroaches are among triggers associated with asthma cases. Literature suggests looking at the areas where individuals spend a considerable amount of time to identify potential exposure sources. Currently, many of these studies have been done regarding the home indoor environment; however, few specifically document the concentrations in carpeting in elementary schools and the exposure time associated with floor-based activities. The objective of this research was to quantify the concentrations of cat (Felis domesticus I), dust mite (Dermatophagoides pteronyssinus I, Dermatophagoides farinae I), and cockroach (Blatella germanica) allergens in carpeting in an elementary school kindergarten class and to document and quantify student group activities that are floor-based. One Florida elementary school classroom was identified as the study site. A total of eight reservoir dust samples were collected during the school year to be analyzed for Felis domesticus I, Dermatophagoides pteronyssinus I, Dermatophagoides farinae I, and Blatella germanica allergens. The sampling reservoir was the carpeting used for group floor-based activities by the school children. Dust samples from the carpet were analyzed by The Johns Hopkins University Reference Laboratory for Dermatology, Allergy, and Clinical Immunology (DACI). The sample collection methodology followed the "Dust Analysis Instructions for Use" provided by the DACI laboratory, along with the "nozzle sock" sampling media. Following discussions with the kindergarten teacher regarding curriculum and scheduled classroom activities, group floor activities were identified. The kindergarten class was observed periodically throughout a school year to document and quantify classroom activities that were floor-based. The information documented includes: occupancy of classroom, occupied floor area, occupant density, and time spent on carpeting. Felis domesticus I (Fel d I) measurements ranged from 2,206 - 10,558 ng of allergen/g of settled dust, Dermatophagoides pteronyssinus I (Der p I) measurements ranged from 3,408 - 86,704 ng/g and Dermatophagoides farinae I (Der f I) measurements ranged from 704 - 6,720 ng/g, and Blatella germanica (Bla g I) measurements were below detection limits. Based upon the DACI criteria, dust mite concentrations were moderate to high and cat concentrations were low to moderate. Kindergarten children spent approximately 38% of classroom time in floor-based activities.