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J Control Release. 2019 Jan 28;294:43-52. doi: 10.1016/j.jconrel.2018.12.008. Epub 2018 Dec 7.

Identification of miRNA-rich vesicles in bronchoalveolar lavage fluid: Insights into the function and heterogeneity of extracellular vesicles.

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Pulmonary Center, Department of Medicine, Boston University Medical Campus, 72 E Concord St., Boston, MA 02118, USA.
Division of Pulmonary and Critical Care Medicine, Department of Medicine, Brigham and Women's Hospital, Boston, MA 02115, USA.
Pulmonary Center, Department of Medicine, Boston University Medical Campus, 72 E Concord St., Boston, MA 02118, USA. Electronic address:


Despite emerging interest in the role of extracellular vesicle (EV)-containing microRNAs (EV-miRNAs), the existence of functional EV-miRNAs under patho-physiological conditions has been viewed with skepticism. Due to the heterogenicity of EVs, several barriers related to EV-miRNA research are to be explored before the in vivo function of EV-miRNAs can be thoroughly delineated. For example, it has been reported that far less than one copy of a given miRNA can be detected per exosome. In this study, we demonstrated that miRNA-rich-EVs exist and can be consistently isolated using differential centrifugation & density-gradient fractionation from bronchoalveolar lavage fluid (BALF) in vivo. The absolute number of this 'miRNA-rich'-EV population is only about 7.05 × 109 per mouse (6% of total EVs). However, the RNA amount detected in this population of EVs represents approximately 39% of the total EV RNAs in the BALF. In contrast, the remaining populations of BALF EVs (76% of total EVs) contain extremely low concentrations of RNAs and miRNAs. The miRNA-rich-EVs in BALF are likely derived from alveolar epithelial type-I cells (ATIs). Notably, caveolin-1, a lipid raft protein, is exclusively detected in the miRNA-rich-EVs, suggesting the lipid raft protein as a biomarker of EV-miRNA enrichment. We further demonstrated that miRNAs contained in the ATI-EVs are actively delivered into alveolar macrophages, subsequently promoting inflammasome activation, neutrophil recruitment, and M1-macrophage polarization in response to P. aeruginosa pneumonia in vitro and in vivo. Collectively, we are the first to identify and characterize the miRNA-rich-EVs in BALF. These miRNA-rich EVs endorse pro-inflammatory responses in bacterial lung infection. Our study provides a novel insight into the development of biomarkers, therapeutic strategies and underlying mechanisms for lung pathology.


Acute lung injury; Bacterial pneumonia; Extracellular vesicles; Lung inflammation; microRNA

[Available on 2020-01-28]

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