Structural and functional characterization of endothelial microparticles released by cigarette smoke.
Sci Rep
; 6: 31596, 2016 08 17.
Article
em En
| MEDLINE
| ID: mdl-27530098
ABSTRACT
Circulating endothelial microparticles (EMPs) are emerging as biomarkers of chronic obstructive pulmonary disease (COPD) in individuals exposed to cigarette smoke (CS), but their mechanism of release and function remain unknown. We assessed biochemical and functional characteristics of EMPs and circulating microparticles (cMPs) released by CS. CS exposure was sufficient to increase microparticle levels in plasma of humans and mice, and in supernatants of primary human lung microvascular endothelial cells. CS-released EMPs contained predominantly exosomes that were significantly enriched in let-7d, miR-191; miR-126; and miR125a, microRNAs that reciprocally decreased intracellular in CS-exposed endothelium. CS-released EMPs and cMPs were ceramide-rich and required the ceramide-synthesis enzyme acid sphingomyelinase (aSMase) for their release, an enzyme which was found to exhibit significantly higher activity in plasma of COPD patients or of CS-exposed mice. The ex vivo or in vivo engulfment of EMPs or cMPs by peripheral blood monocytes-derived macrophages was associated with significant inhibition of efferocytosis. Our results indicate that CS, via aSMase, releases circulating EMPs with distinct microRNA cargo and that EMPs affect the clearance of apoptotic cells by specialized macrophages. These targetable effects may be important in the pathogenesis of diseases linked to endothelial injury and inflammation in smokers.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Fumaça
/
Micropartículas Derivadas de Células
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Produtos do Tabaco
Tipo de estudo:
Observational_studies
/
Risk_factors_studies
Limite:
Animals
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Female
/
Humans
Idioma:
En
Ano de publicação:
2016
Tipo de documento:
Article