title: Epithelial cell-derived microvesicles activate macrophages and promote inflammation via microvesicle-containing microRNAs.
abstract: Intercellular communications between lung epithelial cells and alveolar macrophages play an essential role in host defense against acute lung injury. Hyperoxia-induced oxidative stress is an established model to mimic human lung injury. We show that after hyperoxia-associated oxidative stress, a large amount of extracellular vesicles (EVs) are detectable in bronchoalveolar lavage fluid (BALF) and culture medium of lung epithelial cells. Microvesicles (MVs), but not exosomes (Exos) or apoptotic bodies (Abs), are the main type of EVs found in the early stages after hyperoxia. Among all the MV compositions, small RNAs are altered the most significantly after hyperoxia-associated oxidative stress. We further confirmed that hyperoxia up-regulates the levels of certain specific miRNAs in the epithelial cell-derived MVs, such as the miR-320a and miR-221. Functionally, the hyperoxia-induced epithelial MVs promote macrophage activation in vitro and facilitate the recruitment of immunomodulatory cells in vivo detected in BALF. Using MV as a cargo, delivery of the specific miRNA-enriched epithelial MVs (miR-221 and/or miR-320a) also triggers macrophage-mediated pro-inflammatory effects. Collectively, epithelial cell-derived MVs promote macrophage-regulated lung inflammatory responses via MV-shuttling miRNAs.
authors.affiliation: Division of Pulmonary and Critical Care Medicine, Department of Medicine, Boston University, Boston, MA 02118, USA.
authors.forename: Heedoo
authors.initials: H
authors.lastname: Lee
authors.affiliation: Division of Pulmonary and Critical Care Medicine, Department of Medicine, Boston University, Boston, MA 02118, USA.
authors.forename: Duo
authors.initials: D
authors.lastname: Zhang
authors.affiliation: Division of Pulmonary and Critical Care Medicine, Department of Medicine, Boston University, Boston, MA 02118, USA.
authors.forename: Ziwen
authors.initials: Z
authors.lastname: Zhu
authors.affiliation: Section of Pulmonary, Critical Care and Sleep Medicine, Yale University School of Medicine, New Haven, CT 06519, USA.
authors.forename: Charles S
authors.initials: CS
authors.lastname: Dela Cruz
authors.affiliation: Division of Pulmonary and Critical Care Medicine, Department of Medicine, Boston University, Boston, MA 02118, USA.
authors.forename: Yang
authors.initials: Y
authors.lastname: Jin
mesh_terms: D001992:Bronchoalveolar Lavage Fluid; D004847:Epithelial Cells / Q000166:cytology*; D006801:Humans; D007249:Inflammation / Q000378:metabolism* / Q000503:physiopathology*; D008262:Macrophage Activation; D035683:MicroRNAs / Q000378:metabolism*
chemical_list: D035683:MicroRNAs