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Modulating pro-fibrotic macrophages using yeast beta-glucan microparticles prepared by Pressurized Gas eXpanded
1Department of Medicine, Firestone Institute for Respiratory Health, McMaster University, 50 Charlton Avenue East, L314-5, Hamilton, ON, L8N 4A6, Canada.
Abstract:
Pro-fibrotic M2-like macrophages are widely implicated in the pathogenesis and progression of lung fibrosis due to their production of pro-fibrotic growth factors and cytokines. Yeast beta-glucan (YBG) microparticles have shown potential as immunomodulators that can convert macrophage polarization from a pro-fibrotic phenotype to an anti-fibrotic phenotype through the engagement of the Dectin-1 receptor. However, the processing conditions used to fabricate YBG microparticles can lead to unpredictable immunomodulatory effects. Herein, we report the use of Pressurized Gas eXpanded liquids (PGX) Technology® to fabricate YBG (PGX-YBG) microparticles with higher surface areas, lower densities, and smaller and more uniform size distributions compared to commercially available spray-dried YBGs. PGX-YBG is shown to activate Dectin-1 more efficiently in vitro while avoiding significant TLR 2/4 activation. Furthermore, PGX-YBG microparticles effectively modulate M2-like fibrosis-inducing murine and human macrophages into fibrosis-suppressing macrophages both in vitro as well as in ex vivo precision-cut murine lung slices, suggesting their potential utility as a therapeutic for addressing a broad spectrum of fibrotic end-point lung diseases.
Insights
Yeast beta-glucan (YBG) microparticles processed with new technology show promise for treating lung fibrosis. These microparticles effectively reprogram pro-fibrotic macrophages into anti-fibrotic ones, offering a potential therapeutic strategy.
Area of Science:
- Immunology
- Biomaterials Science
- Pulmonary Medicine
Background:
- Pro-fibrotic M2-like macrophages drive lung fibrosis through growth factor and cytokine production.
- Yeast beta-glucan (YBG) microparticles can modulate macrophage polarization via Dectin-1 receptor engagement.
- Current YBG microparticle fabrication methods yield unpredictable immunomodulatory outcomes.
Purpose of the Study:
- To develop YBG microparticles with enhanced properties for improved immunomodulation.
- To investigate the efficacy of PGX-YBG microparticles in modulating macrophage polarization.
- To assess the therapeutic potential of PGX-YBG for lung fibrotic diseases.
Main Methods:
- Fabrication of YBG microparticles using Pressurized Gas eXpanded liquids (PGX) Technology.
- Characterization of PGX-YBG microparticles (surface area, density, size distribution).
- In vitro and ex vivo assessment of macrophage polarization and Dectin-1/TLR activation.
Main Results:
- PGX-YBG microparticles exhibited higher surface areas, lower densities, and more uniform size distributions than spray-dried YBGs.
- PGX-YBG demonstrated more efficient Dectin-1 activation with minimal TLR 2/4 activation in vitro.
- PGX-YBG effectively converted M2-like fibrotic macrophages to a fibrosis-suppressing phenotype in vitro and ex vivo.
Conclusions:
- PGX Technology enables the fabrication of YBG microparticles with superior physicochemical and immunomodulatory properties.
- PGX-YBG microparticles represent a promising therapeutic agent for lung fibrosis by reprogramming pro-fibrotic macrophages.
- This approach holds potential for treating diverse fibrotic lung diseases.
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