Skip navigation
  • Home
  • Browse
    • Communities
      & Collections
    • Browse Items by:
    • Publication Date
    • Author
    • Title
    • Subject
    • Department
  • Sign on to:
    • My MacSphere
    • Receive email
      updates
    • Edit Profile


McMaster University Home Page
  1. MacSphere
  2. Open Access Dissertations and Theses Community
  3. Open Access Dissertations and Theses
Please use this identifier to cite or link to this item: http://hdl.handle.net/11375/27162
Full metadata record
DC FieldValueLanguage
dc.contributor.advisorAsk, Kjetil-
dc.contributor.authorImran Hayat, Aaron-
dc.date.accessioned2021-11-10T16:18:55Z-
dc.date.available2021-11-10T16:18:55Z-
dc.date.issued2021-
dc.identifier.urihttp://hdl.handle.net/11375/27162-
dc.description.abstractIdiopathic Pulmonary Fibrosis (IPF) is a debilitating respiratory disorder that is characterized by a progressive decline in lung function. Originating through unknown etiology, it is essentially an unchecked wound healing response that causes the build-up of excessive scar tissue in the lung interstitial tissue with a heavy toll on the patient’s respiratory capacity. Pro-fibrotic alternatively activated macrophages (M2) have been linked as an important contributor to the fibrotic remodeling of the lung. Previous Ask research indicates that targeting M2 macrophages is possible through the use of the Dectin-1 receptor, a transmembrane cell surface receptor found in high abundance on M2 macrophages. Activating the Dectin-1 receptor through the use of beta-glucan, a ligand the receptor has a high affinity for, initiates a pro-inflammatory response within the naturally immunosuppressive macrophage and can alter its activity to be less fibrogenic. Our data suggest that M2 polarization of naïve macrophages can be inhibited in vitro by beta-glucan microparticles. Additionally, we have found that polarized M2 macrophages adopt M1-like characteristics when treated with beta-glucan microparticles, in a process that is largely Dectin-1 dependent. M2 cell surface marker CD206, increased levels of which are associated with rapidly progressing IPF, shows significantly decreased frequency of expression in M2 macrophages treated with beta-glucan microparticles. Our assessment for cell-specific uptake of beta-glucan microparticles suggests an important role of the Dectin-1 receptor for significantly increased uptake in murine wild-type M2 macrophages relative to their Dectin-1 knockout counterpart. The use of beta-glucan microparticles as a potential anti-fibrotic therapeutic was assessed in the bleomycin model of fibrotic lung disease. Mice given bleomycin and treated with beta-glucan displayed decreased soluble collagen content and TGFB expression within lung homogenate relative to fibrotic bleomycin control mice. Overall, these results provide insight into the use of beta-glucan as a potential activity modulator of macrophage function in IPF and the possibility of its use as a therapeutic.en_US
dc.language.isoenen_US
dc.subjectIdiopathic pulmonary fibrosis, IPF, Alternatively activated macrophage, M2, M1, Classically activated macrophage, Interstitial lung disease, Fibrotic lung disease, Bone-Marrow Derived Macrophage, IHC, TGF-B, Transforming growth factor beta, beta-glucan, microparticle, yeast-derived beta glucan, bleomycinen_US
dc.titleTargeting the Dectin-1 Receptor via Beta-Glucan Microparticles to Modulate Alternatively Activated Macrophage Activity and Inhibit Alternative Activationen_US
dc.title.alternativeINFLUENCING PROFIBROTIC MACROPHAGE POLARIZATION AND ACTIVITY USING YEAST-DERIVED MICROPARTICLESen_US
dc.typeThesisen_US
dc.contributor.departmentMedical Sciencesen_US
dc.description.degreetypeThesisen_US
dc.description.degreeMaster of Science (MSc)en_US
Appears in Collections:Open Access Dissertations and Theses

Files in This Item:
File Description SizeFormat 
TARGETING THE DECTIN-1 RECEPTOR VIA BETA-GLUCAN MICROPARTICLES TO MODULATE ALTERNATIVELY ACTIVATED MACROPHAGE ACTIVITY AND INHIBIT ALTERNATIVE ACTIVATION.pdf
Access is allowed from: 2022-10-07
3.57 MBAdobe PDFView/Open
Show simple item record Statistics


Items in MacSphere are protected by copyright, with all rights reserved, unless otherwise indicated.

Sherman Centre for Digital Scholarship     McMaster University Libraries
©2022 McMaster University, 1280 Main Street West, Hamilton, Ontario L8S 4L8 | 905-525-9140 | Contact Us | Terms of Use & Privacy Policy | Feedback

Report Accessibility Issue