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An in vivo model for extracellular vesicle-induced emphysema.
Margaroli, Camilla; Madison, Matthew C; Viera, Liliana; Russell, Derek W; Gaggar, Amit; Genschmer, Kristopher R; Blalock, J Edwin.
Affiliation
  • Margaroli C; Department of Medicine, Division of Pulmonary, Allergy and Critical Care Medicine.
  • Madison MC; Program in Protease and Matrix Biology, and.
  • Viera L; Department of Medicine, Division of Pulmonary, Allergy and Critical Care Medicine.
  • Russell DW; Program in Protease and Matrix Biology, and.
  • Gaggar A; Department of Medicine, Division of Pulmonary, Allergy and Critical Care Medicine.
  • Genschmer KR; Department of Medicine, Division of Pulmonary, Allergy and Critical Care Medicine.
  • Blalock JE; Program in Protease and Matrix Biology, and.
JCI Insight ; 7(4)2022 01 25.
Article in En | MEDLINE | ID: mdl-35077395
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.
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Pulmonary Emphysema / Pulmonary Disease, Chronic Obstructive / Extracellular Vesicles Type of study: Diagnostic_studies / Prognostic_studies Limits: Animals Language: En Journal: JCI Insight Year: 2022 Document type: Article

Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Pulmonary Emphysema / Pulmonary Disease, Chronic Obstructive / Extracellular Vesicles Type of study: Diagnostic_studies / Prognostic_studies Limits: Animals Language: En Journal: JCI Insight Year: 2022 Document type: Article