Extracellular Vesicle: An Unknown Environmental Factor for Causing Airway Disease

179 Most cells from different organisms release extracellular vesi-cles (EVs) to the extracellular environment. The term EV is a broad one for all types of vesicles found in body fluids and cell culture in accordance with the recommendation of the International Society for Extracellular Vesicles (ISEV). 1 In recent years, Interest in EVs increased because of their function in intercellu-lar communication and their potential use as biomarkers and therapeutics for several diseases. These EVs contain various DNAs, proteins, mRNAs, and mi-croRNAs (miRNAs) that have potential diagnostic and therapeutic implications and are classified into exosomes, microves-icles, and apoptotic bodies through their biogenesis and secretion mechanisms. Exosomes are 50 to 150-nm vesicles released by living cells. Microvesicles are 100-to 2,000-nm vesicles formed by direct outward budding of the plasma membrane from living cells. Apoptotic bodies are 1-to 4-μm vesicles and released from the plasma membrane as apoptotic cell blebs. 4 EVs act as a signaling complex, transfer membrane receptors between cells, deliver proteins to target cells, and modify the receiving cells by horizontal transfer of genetics. 5 Many studies have suggested that EVs might be involved in a wide range of biological processes, including immune regulation , inflammation, and tumor development. 6 EV have been isolated from different body fluids, such as plasma, 7 urine, 8 and bronchoalveolar lavage fluid (BALF). 9 EVs are highly stable in biological fluids and protected from degradation by their lipid bilayer. 4 They play important roles in maintaining homeostasis through intercellular communication in the human airway. Recently, their biological roles draw significant interest in respiratory diseases because their contents, including miRNA, play an important role in the pathogenesis of many respiratory diseases, including lung cancer, interstitial lung disease, chronic obstructive pulmonary disease, and allergic diseases like asthma. EVs can potentially control lung and airway inflammation through intercellular communication. Exposure to various stimuli, such as infection, DNA damage, and smoke exposure, enhances EV secretion and modify EV composition to change the surrounding microenvironment through EV-mediated cell-to-cell communication. Noncancerous cell-derived EVs in the airway show protective functions against injuries, such as tissue recovery and repair, but lung cancer-derived EVs regulate tumor malignancy. 14 Exo-some secretion is increased during allergic inflammation in the lungs, which may mediate increased intercellular signaling. 6 A few studies have reported that EVs may regulate airway inflammation and allergic reactions through their paracrine effects in the lungs. 15,16 BALF exosomes from healthy individuals and …