SARS-CoV-2 treatment effects induced by ACE2-expressing microparticles are explained by the oxidized cholesterol-increased endosomal pH of alveolar macrophages.
Cell Mol Immunol
; 19(2): 210-221, 2022 02.
Article
in English
| MEDLINE | ID: covidwho-1608557
ABSTRACT
Exploring the cross-talk between the immune system and advanced biomaterials to treat SARS-CoV-2 infection is a promising strategy. Here, we show that ACE2-overexpressing A549 cell-derived microparticles (AO-MPs) are a potential therapeutic agent against SARS-CoV-2 infection. Intranasally administered AO-MPs dexterously navigate the anatomical and biological features of the lungs to enter the alveoli and are taken up by alveolar macrophages (AMs). Then, AO-MPs increase the endosomal pH but decrease the lysosomal pH in AMs, thus escorting bound SARS-CoV-2 from phago-endosomes to lysosomes for degradation. This pH regulation is attributable to oxidized cholesterol, which is enriched in AO-MPs and translocated to endosomal membranes, thus interfering with proton pumps and impairing endosomal acidification. In addition to promoting viral degradation, AO-MPs also inhibit the proinflammatory phenotype of AMs, leading to increased treatment efficacy in a SARS-CoV-2-infected mouse model without side effects. These findings highlight the potential use of AO-MPs to treat SARS-CoV-2-infected patients and showcase the feasibility of MP therapies for combatting emerging respiratory viruses in the future.
Keywords
Full text:
Available
Collection:
International databases
Database:
MEDLINE
Main subject:
Endosomes
/
Cholesterol
/
Macrophages, Alveolar
/
Cell-Derived Microparticles
/
Cell- and Tissue-Based Therapy
/
Angiotensin-Converting Enzyme 2
/
SARS-CoV-2
/
COVID-19
Type of study:
Experimental Studies
/
Prognostic study
/
Randomized controlled trials
Limits:
Animals
/
Female
/
Humans
Language:
English
Journal:
Cell Mol Immunol
Journal subject:
Allergy and Immunology
Year:
2022
Document Type:
Article
Affiliation country:
S41423-021-00813-6
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