Exosomes mediate interepithelial transfer of functional P-glycoprotein in chronic rhinosinusitis with nasal polyps.
Laryngoscope
; 127(9): E295-E300, 2017 09.
Article
in En
| MEDLINE
| ID: mdl-28485529
ABSTRACT
OBJECTIVE:
P-glycoprotein (P-gp) drives type-2 helper T-cell inflammation in chronic rhinosinusitis with nasal polyps (CRSwNP) through unknown posttranslational mechanisms of overexpression. A recent randomized clinical trial demonstrated that inhibition of P-gp was as effective as oral steroids and biologics in treating CRSwNP. Exosomes are 30- to 150-nm vesicles capable of intercellular membrane protein transfer. The aims of this study were 1) to determine whether CRSwNP mucus exosomes are enriched with P-gp, and 2) whether exosomal P-gp can be functionally transferred to autologous epithelial cells as a putative mechanism for the proinflammatory overexpression of P-gp in CRSwNP. STUDYDESIGN:
Institutional review board-approved study in CRSwNP and control patients (n = 10 per group).METHODS:
P-gp content of purified mucus exosomes was characterized by transmission electron microscopy and enzyme-linked immunosorbent assay. Epithelial transfer of exosomal P-gp was determined by time-lapse fluorescent microscopy and calcein acetoxymethylester functional P-gp assay.RESULTS:
CD63+/P-gp+ exosomes were detected in both groups. P-gp was significantly enriched in CRSwNP exosomes relative to control (median 198.5; interquartile range 123.6-270.5 vs. 74.4; 41.3-95.0 pcg P-gp/109 exosomes, P = 0.002). Exosomes were absorbed by epithelial cells within 10 minutes, resulting in a significant increase in P-gp activity in CRSwNP patients relative to control (P = 0.006).CONCLUSION:
Here we demonstrate the presence and P-gp enrichment of mucus-derived exosomes, or rhinosomes, in CRSwNP. These rhinosomes are capable of rapid intercellular transfer of P-gp, leading to increased P-gp function within recipient cells. This represents a novel mechanism for maintaining P-gp overexpression in CRSwNP, and more generally for interepithelial transfer of other proteins between mucosal epithelial cells. LEVEL OF EVIDENCE NA. Laryngoscope, 127E295-E300, 2017.Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Sinusitis
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Rhinitis
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Nasal Polyps
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ATP Binding Cassette Transporter, Subfamily B, Member 1
/
Exosomes
Type of study:
Clinical_trials
/
Observational_studies
Limits:
Adult
/
Aged
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Female
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Humans
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Male
/
Middle aged
Language:
En
Journal:
Laryngoscope
Journal subject:
OTORRINOLARINGOLOGIA
Year:
2017
Document type:
Article
Affiliation country:
United States
Publication country:
EEUU
/
ESTADOS UNIDOS
/
ESTADOS UNIDOS DA AMERICA
/
EUA
/
UNITED STATES
/
UNITED STATES OF AMERICA
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US
/
USA