University of SaskatchewanHARVEST
  • Login
  • Submit Your Work
  • About
    • About HARVEST
    • Guidelines
    • Browse
      • All of HARVEST
      • Communities & Collections
      • By Issue Date
      • Authors
      • Titles
      • Subjects
      • This Collection
      • By Issue Date
      • Authors
      • Titles
      • Subjects
    • My Account
      • Login
      JavaScript is disabled for your browser. Some features of this site may not work without it.
      View Item 
      • HARVEST
      • Electronic Theses and Dissertations
      • Graduate Theses and Dissertations
      • View Item
      • HARVEST
      • Electronic Theses and Dissertations
      • Graduate Theses and Dissertations
      • View Item

      Mechanisms of Lung Inflammation Following Exposure to Swine Barn Air

      Thumbnail
      View/Open
      Charavaryamath_C_Thesis.pdf (6.173Mb)
      Date
      2008
      Author
      Charavaryamath, Chandrashekhar
      Type
      Thesis
      Degree Level
      Doctoral
      Metadata
      Show full item record
      Abstract
      Occupational 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.
      Degree
      Doctor of Philosophy (Ph.D.)
      Department
      Veterinary Biomedical Sciences
      Program
      Veterinary Biomedical Sciences
      Supervisor
      Singh, Baljit
      Committee
      Mutwiri, George; Townsend, Hugh; Koehncke, Niels; Hiebert, Linda; Fox-Robichaud, Alison
      Copyright Date
      2008
      URI
      http://hdl.handle.net/10388/etd-09042008-124233
      Subject
      lung
      N-myristoyltransferase
      swine barn air
      lipopolysaccharide
      calcineurin
      Toll-like receptor-4
      inflammation
      occupational lung disease
      airway hyperresponsiveness
      Collections
      • Graduate Theses and Dissertations
      University of Saskatchewan

      University Library

      © University of Saskatchewan
      Contact Us | Disclaimer | Privacy