An in vivo model for extracellular vesicle-induced emphysema.
JCI Insight
; 7(4)2022 01 25.
Article
en En
| MEDLINE
| ID: mdl-35077395
ABSTRACT
Chronic obstructive pulmonary disease (COPD) is a debilitating chronic disease and the third-leading cause of mortality worldwide. It is characterized by airway neutrophilia, promoting tissue injury through release of toxic mediators and proteases. Recently, it has been shown that neutrophil-derived extracellular vesicles (EVs) from lungs of patients with COPD can cause a neutrophil elastase-dependent (NE-dependent) COPD-like disease upon transfer to mouse airways. However, in vivo preclinical models elucidating the impact of EVs on disease are lacking, delaying opportunities for therapeutic testing. Here, we developed an in vivo preclinical mouse model of lung EV-induced COPD. EVs from in vivo LPS-activated mouse neutrophils induced COPD-like disease in naive recipients through an α-1 antitrypsin-resistant, NE-dependent mechanism. Together, these results show a key pathogenic and mechanistic role for neutrophil-derived EVs in a mouse model of COPD. Broadly, the in vivo model described herein could be leveraged to develop targeted therapies for severe lung disease.
Palabras clave
Texto completo:
1
Base de datos:
MEDLINE
Asunto principal:
Enfisema Pulmonar
/
Enfermedad Pulmonar Obstructiva Crónica
/
Vesículas Extracelulares
Tipo de estudio:
Diagnostic_studies
/
Prognostic_studies
Idioma:
En
Revista:
JCI Insight
Año:
2022
Tipo del documento:
Article