4.7 Article

Particulate β-glucan activates early and delayed phagosomal maturation and autophagy within macrophage in a NOX-2 dependent manner

期刊

LIFE SCIENCES
卷 266, 期 -, 页码 -

出版社

PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.lfs.2020.118851

关键词

beta-Glucan; Microparticles; NOX-2; Reactive oxygen species; Autophagy; Antibacterial activity

资金

  1. University Grants Commission (UGC)
  2. U.P. Council of Science and Technology (UPCST) [CST/D-1588]
  3. Integral University [IU/RD/2017-MCN00018]

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Certain microparticles, such as YDGP, are capable of inducing NOX-2-dependent autophagy and antimicrobial activity, showing potential as therapeutic agents in the future.
Aims: Macrophage is known to readily engulf any particulate material they encounter, including invading microbes and nano- or micro-particles. While recent studies show that some microparticles (MP) are immunogenic even without drug-cargo, the mechanism underlying this phenomenon is yet unclear. Phagocytosis induces NADPH oxidase-2 (NOX-2) mediated ROS generation that is reported to regulate antibacterial autophagy. We therefore, investigated the role of NOX-2 derived ROS in phagosomal maturation and autophagy induction in response to phagocytic uptake of two kinds of polymeric biodegradable and biocompatible microparticles: yeast-derived beta-glucan particles (YDGP) and poly-(D, L-Lactic Acid) microparticles (PMP). Main methods: J774A.1 macrophage wereas exposed to polymeric particles and the immune responses: ROS, phagosomal maturation and autophagy induction, were examined by assays including NBT, DCFH-DA, NADPH-Oxidase activity, Lysotracker and Acridine Orange. Further, the LC3 and NOX-2 expression were validated by RT-PCR, immunofluorescence assay and Western blotting. Antimicrobial activity of both MP was examined by CFU counting after administration to Mycobacterium tuberculosis and Salmonella typhimurium infected macrophage. Key findings: YDGP induces phagosomal maturation and acidic vesicle accumulation at 30 min and 24 h postexposure, much more proficiently than that by PMP. YDGP exposure also induced NOX-2 dependent expression of light chain 3 (LC3-II), further confirmed as autophagy activation via autophagic flux assay with autophagolysosome inhibitor bafilomycin Al . Additionally, YDGP displayed superior anti-microbial activity than that by PMP. Significance: The induction of NOX-2-dependent autophagy and antimicrobial activity exhibited by particulate glucans has significant implications in harnessing these drug delivery vehicles as potential 'value-added' autophagy-mediated therapeutics in future.

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