Extracellular vesicles: novel communicators in lung diseases

Abstract

The lung is the organ with the highest vascular density in the human body. It is therefore perceivable that the endothelium of the lung contributes significantly to the circulation of extracellular vesicles (EVs), which include exosomes, microvesicles, and apoptotic bodies. In addition to the endothelium, EVs may arise from alveolar macrophages, fibroblasts and epithelial cells. Because EVs harbor cargo molecules, such as miRNA, mRNA, and proteins, these intercellular communicators provide important insight into the health and disease condition of donor cells and may serve as useful biomarkers of lung disease processes. This comprehensive review focuses on what is currently known about the role of EVs as markers and mediators of lung pathologies including COPD, pulmonary hypertension, asthma, lung cancer and ALI/ARDS. We also explore the role EVs can potentially serve as therapeutics for these lung diseases when released from healthy progenitor cells, such as mesenchymal stem cells. Extracellular vesicles Cell-to-cell communication is essential for nearly all physiologic and metabolic processes. This intercellular conveyance is achieved through receptor ligands, signaling molecules, hormones, and extracellular vesicles (EVs). Historically, secretion of the cell in the form of EVs was considered as unimportant waste material, cellular "garbage bags," or dust particles [1-5]. However, in recent years, this so-called "waste" is now known to be of profound importance in various biological systems, creating a boon in their exploration across the scientific community. Lipid bilayer membrane-enclosed vesicles are secreted by both prokaryotic and eukaryotic cells [4-9]. Although, the term "extracellular vesicle" is sometimes used in reference to exosomes, it is actually a very broad term that encompasses all different types of vesicles secreted outside the cells [10]. Regardless, the function of all these vesicles appears to be all the same: communication between the cells within an organism or between species [11, 12]. In addition, it is not necessary that all vesicles secreted from cells are functional or have any role in some kind of biological process. Sometimes, they just act as "dustcart" to remove the waste from cells [13]. Of note, there have been discrepancies in the classification of these vesicles in the literature. Some studies divide EVs into two major categories: I) exosomes, defined as vesicles released by exocytosis of the multivesicular bodies; and II) ectosomes, defined as the vesicles which are assembled and released by the plasma membrane [14]. However, most recent studies categorize EVs as either exosome, microvesicles, microparticles, or apoptotic bodies based on vesicle size and how they are formed [15-21] (Fig. 1). Exosomes Exosomes are small EVs with sizes ranging between 30 and 150 nm in diameter that originate from the internal vesicles of multivesicular bodies (MVB) of nearly all cell types. Exosomes originating from different cell types have different composition; however, there are certain

The Potential Role of Extracellular Vesicles in COVID-19 Associated Endothelial injury and Pro-inflammation

“…Extracellular vesicles play a key role in the pathogenesis of various diseases, including acute respiratory distress syndrome (ARDS), chronic obstructive pulmonary disease (COPD) pulmonary hypertension (PH), and sepsis (8). Furthermore, EVs released by virus-infected cells can transfer viral proteins, viral receptors, and pro-inflammatory cargo to recipient cells, thereby contributing to the spread of viral infection and worsening tissue injury (9).…”

The Role of T Cells and Macrophages in Asthma Pathogenesis: A New Perspective on Mutual Crosstalk

“…EVs in the lung are primarily derived from epithelial cells and macrophages [ 145 ], which can be detected in the sputum and BALF of asthmatic patients [ 146 ]. Mohan et al [ 147 ] discovered that exosomal miRNAs (miRNA-let-7a, miRNA-21, miRNA-658, miRNA-24, miRNA-26a, miRNA-99a, miRNA-200c, and miRNA-1268) lay a great difference between asthmatic patients and healthy controls, possibly related to the severity of the allergy and the lung function. Several EVs are able to control macrophage differentiation.…”

Hypertonic saline solution inhibits SARS-CoV-2 in vitro assay

“…Vesicle formation is important for kidney and lung cells as responses to alteration of osmosis, regulated by aquaporin channels 17 , as well as for vesicle transfer between cells, which has been suggested to contribute to lung disease and possibly to the propagation of the SARS-CoV-2 virus into neighboring cells 18 .…”