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http://hdl.handle.net/11375/27162
Title: | Targeting the Dectin-1 Receptor via Beta-Glucan Microparticles to Modulate Alternatively Activated Macrophage Activity and Inhibit Alternative Activation |
Other Titles: | INFLUENCING PROFIBROTIC MACROPHAGE POLARIZATION AND ACTIVITY USING YEAST-DERIVED MICROPARTICLES |
Authors: | Imran Hayat, Aaron |
Advisor: | Ask, Kjetil |
Department: | Medical Sciences |
Keywords: | Idiopathic 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, bleomycin |
Publication Date: | 2021 |
Abstract: | Idiopathic 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. |
URI: | http://hdl.handle.net/11375/27162 |
Appears in Collections: | Open Access Dissertations and Theses |
Files in This Item:
File | Description | Size | Format | |
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TARGETING THE DECTIN-1 RECEPTOR VIA BETA-GLUCAN MICROPARTICLES TO MODULATE ALTERNATIVELY ACTIVATED MACROPHAGE ACTIVITY AND INHIBIT ALTERNATIVE ACTIVATION.pdf | 3.57 MB | Adobe PDF | View/Open |
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