Extracellular Vesicles Facilitate the Intercellular Communications in the Pathogenesis of Lung Injury

Abstract

Extracellular vesicles (EVs) are a group of heterogeneous, nano-sized structures surrounded by lipid bilayer membranes that are released by cells. Depending on their size and mechanisms of formation, EVs are often referred to as exosomes, microvesicles (MVs) and apoptotic bodies (AB). EVs are evolutionally conserved vesicles that mediate intercellular communications and cross-talk, via transferring proteins, lipids and nucleic acids. Accumulating evidence suggests that EVs exert essential physiological and pathological functions on both their mother and recipient cells. Therefore, growing interests focus on the potentials of EVs to serve as novel targets for the development of therapeutic and diagnostic strategies. Currently, extensive reports are yielded from cancer research. However, besides malignancy, EVs may also serve as crucial regulators in other devastating conditions, such as the acute respiratory distress syndrome (ARDS) and acute lung injury (ALI). The generation, regulation and function of EVs in ARDS/ALI are largely unexplored. In this mini review, we will briefly review the current understanding of EVs and their known physiological/pathological functions in the pathogenesis of ARDS/ALI. Previously, only scattered reports have been published in this field. We believe that further investigations focusing on EVs and their compositions will shed light on novel insights in the research of ARDS/ALI.

Lung Epithelial Cell–Derived Microvesicles Regulate Macrophage Migration via MicroRNA-17/221–Induced Integrin β1 Recycling

“…Whereas the release of MVs is continuous, and stimulated by a variety of cell stressor, ABs are only generated as a result of cell death. In contrast MVs and Exos are continuously released by live cells (7, 8) in either the absence or presence of noxious stimuli (9, 10). Recent studies have shown that both proteins and nucleic acids are differentially sorted into the three types of EVs reflecting their functional diversity (3, 9).…”

“…Accumulating evidence further suggest that in addition to EV surface antigens, EV can shuttle microRNAs (miRNAs) that may play an essential role in mediating intercellular communication (11–13). It is now generally accepted that single miRNAs have diverse targets and can up- or down-regulate hundreds of genes (14), MVs and Exos therefore act in part as messengers in the coordination of innate immune responses to noxious stimuli (7, 9, 10). …”

“…Common features of ALI/ARDS include an intense inflammatory response in the lung parenchyma, severe injury to the epithelial and endothelial cell barriers leading to alveolar edema, decreased lung compliance, impaired gas exchange and hypoxemia (17, 18). This can occur in the presence of a broad range of agents including oxidative stress, acid aspiration and infection (7, 10). The alveolar epithelium functions as a first-line defense against noxious insults and as such is critical in maintaining the integrity and function of the lung during development of ALI (17–20).…”

Purification and characterization of microRNAs within middle ear fluid exosomes: implication in otitis media pathophysiology

“…Importantly, in parallel respiratory diseases, such as chronic lung diseases, epithelial derived exosomes have been shown to drive local inflammation through significant macrophage and neutrophil activation (25). Further, these events serve as crucial mediators of acute lung injury (26). Whether similar processes could be going on in OM pathophysiology remains mostly unexplored and is the impetus for our work, but neutrophilic inflammation appears to be key in OM disease development (9).…”

Personalized medicine and back–allogeneic exosomes for cancer immunotherapy

“…The cells of the immune system communicate by different means such as soluble factors, cell surface molecules and extracellular vesicles (EV). Exosomes are nanosized cell-derived EVs that are known to play critical roles in intercellular communication [4]. Prior to the understanding of their immunological functions, they were considered as insignificant cell garbage bags.…”