Extracellular vesicles released in response to respiratory exposures

Extracellular vesicles (EV) are secreted signaling entities that enhance various pathological processes when released in response to cellular stresses. Respiratory exposures such as cigarette smoke and air pollution exert cellular stresses and are associated with an increased risk of several chronic diseases. Researchers from Maastricht University Medical Center examine the evidence that modifications in EV contribute to respiratory exposure-associated diseases. Fifty articles were identified, most of which investigated the effect of respiratory exposures on EV release in vitro (25) and/or on circulating EV in human plasma (24). The majority of studies based their main observations on the relatively insensitive scatter-based flow cytometry of EV (29). EV induced by respiratory exposures were found to modulate inflammation (19), thrombosis (13), endothelial dysfunction (11), tissue remodeling (6), and angiogenesis (3). By influencing these processes, EV may play a key role in the development of cardiovascular diseases and chronic obstructive pulmonary disease and possibly lung cancer and allergic asthma. The current findings warrant additional research with improved methodologies to evaluate the contribution of respiratory exposure-induced EV to disease etiology, as well as their potential as biomarkers of exposure or risk and as novel targets for preventive or therapeutic strategies.

Schematic representation of how respiratory exposure-induced EV
may contribute to the pathogenesis of chronic diseases


Respiratory toxicants arise from CS, as well as occupational or environmental sources. Upon inhalation, they come in contact with several cell types of the lungs, including epithelial cells, endothelial cells, alveolar macrophages, monocytes, and circulating blood cells. Exposure to respiratory toxicants causes increased release and altered composition of EV from different cellular sources. The respiratory exposure-induced EV may either remain in the lung lumen or are disseminated via the blood circulation. Locally at the site of exposure as well as systemically, they may promote inflammation, hypercoagulability, endothelial dysfunction, tissue remodeling, and angiogenesis, all of which are interrelated and can further enhance each other. By promoting these biological processes, EV may contribute to the mechanistic link between respiratory exposures and the pathogenesis of respiratory exposure-associated diseases such as COPD, CVD, asthma, and lung cancer. For each biological process, the diseases are sorted according to the strength of evidence for involvement of the respective process in their pathogenesis.

Benedikter BJ, Wouters EFM, Savelkoul PHM, Rohde GGU, Stassen FRM. (2018) Extracellular vesicles released in response to respiratory exposures: implications for chronic disease. J Toxicol Environ Health B Crit Rev [Epub ahead of print]. [article]

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