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dc.contributor.advisorSingh, Baljiten_US
dc.creatorCharavaryamath, Chandrashekharen_US
dc.date.accessioned2008-09-04T12:42:33Zen_US
dc.date.accessioned2013-01-04T04:56:31Z
dc.date.available2009-09-06T08:00:00Zen_US
dc.date.available2013-01-04T04:56:31Z
dc.date.created2008en_US
dc.date.issued2008en_US
dc.date.submitted2008en_US
dc.identifier.urihttp://hdl.handle.net/10388/etd-09042008-124233en_US
dc.description.abstractOccupational exposure to endotoxin-rich swine barn air induces respiratory diseases and loss of lung function. Barn exposure induces recruitment of pulmonary intravascular monocytes/macrophages (PIMMs) and subsequent increased host sensitivity to Escherichia coli LPS challenge. Therefore, to further clarify the biology of PIMMs we examined the role of recruited PIMMs in a rat Escherichia coli-induced lung inflammation model. Following sepsis, lung inflammation was induced with recruitment of PIMMs and subsequently, Escherichia coli LPS challenge exacerbated the lung inflammation with localization of multiple inflammatory cytokines in PIMMs to suggest their possible involvement in modulating lung inflammation in this model. In order to delineate mechanisms of barn air induced lung dysfunction, a rat model of occupational exposure was characterized to show that one and five exposures to the barn environment induced acute lung inflammation and increased airway hyperresponsiveness (AHR). Following 20 exposures, AHR was dampened to indicate adaptive responses. Barn air contains high levels of endotoxin which led us to investigate its role in lung inflammation and AHR. Exposure of mice with either a functional TLR4 (WT) or non-functional TLR4 (mutants) to barn air revealed dependence of lung inflammation but not AHR on a functional TLR4. I investigated whether exposure to barn air alters host responses to a subsequent microbial challenge. Following one day barn exposure and Escherichia coli LPS challenge, lung inflammation was exacerbated with increased granulocytes and IL-1β levels compared to one day barn exposed rats without Escherichia coli LPS challenge. However, increased granulocytes and IL-1β levels in barn exposed and Escherichia coli LPS challenged rats were not different from control rats treated with Escherichia coli LPS indicating a lack of priming effect of barn exposure. However, above results are suggestive of an underlying risk of increased lung inflammation following secondary microbial infection in naïve barn workers. Lastly, I investigated the expression and activity of novel signalling molecules called N-myristoyltransferase and calcineurin in barn air and E. coli LPS induced lung inflammation models. Following one day barn exposure, increased protein expression but not activity of N-myristoyltransferase and calcineurin was shown. However, there is a need to identify the specific role of these two molecules in barn air induced lung inflammation. To conclude, animal models of barn exposure are useful tools to understand mechanisms of lung inflammation and AHR. However, there is still a need to examine endotoxin-independent nature of AHR and roles of other molecules of the innate immune system in regulating barn air induced effects.en_US
dc.language.isoen_USen_US
dc.subjectlungen_US
dc.subjectN-myristoyltransferaseen_US
dc.subjectswine barn airen_US
dc.subjectlipopolysaccharideen_US
dc.subjectcalcineurinen_US
dc.subjectToll-like receptor-4en_US
dc.subjectinflammationen_US
dc.subjectoccupational lung diseaseen_US
dc.subjectairway hyperresponsivenessen_US
dc.titleMechanisms of Lung Inflammation Following Exposure to Swine Barn Airen_US
thesis.degree.departmentVeterinary Biomedical Sciencesen_US
thesis.degree.disciplineVeterinary Biomedical Sciencesen_US
thesis.degree.grantorUniversity of Saskatchewanen_US
thesis.degree.levelDoctoralen_US
thesis.degree.nameDoctor of Philosophy (Ph.D.)en_US
dc.type.materialtexten_US
dc.type.genreThesisen_US
dc.contributor.committeeMemberMutwiri, Georgeen_US
dc.contributor.committeeMemberTownsend, Hughen_US
dc.contributor.committeeMemberKoehncke, Nielsen_US
dc.contributor.committeeMemberHiebert, Lindaen_US
dc.contributor.committeeMemberFox-Robichaud, Alisonen_US


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