Extracellular Vesicles: A New Frontier for Research in Acute Respiratory Distress Syndrome

Abstract

Recent research on extracellular vesicles (EVs) has provided new insights into pathogenesis and potential therapeutic options for acute respiratory distress syndrome (ARDS). EVs are membrane-bound anuclear structures that carry important intercellular communication mechanisms, allowing targeted transfer of diverse biologic cargo, including protein, mRNA, and microRNA, among several different cell types. In this review, we discuss the important role EVs play in both inducing and attenuating inflammatory lung injury in ARDS as well as in sepsis, the most important clinical cause of ARDS. We discuss the translational challenges that need to be overcome before EVs can also be used as prognostic biomarkers in patients with ARDS and sepsis. We also consider how EVs may provide a platform for novel therapeutics in ARDS.

Keywords: acute lung injury; acute respiratory distress syndrome; extracellular vesicles; sepsis.

Figure 1.

Cell-specific extracellular vesicles (EVs) and their cargo in acute respiratory distress syndrome (ARDS). EV shown with phospholipid bilayer and potential cargo. EV cargo can include microRNA, mRNA, mitochondria, and protein (e.g., cytokines). (Upper panel) Pathogenic EVs and their cargo. (Lower panel) Protective EVs and their cargo. EV parent cells are identified by surface marker expression (e.g., CD31⁺ indicates endothelial-derived, CD14⁺ indicates monocyte-derived, CD206⁺ indicates alveolar macrophage–derived, CD326⁺ indicates epithelial-derived, CD66b⁺ indicates neutrophil-derived, and CD90/105/73⁺ indicates mesenchymal stromal cell–derived EV). Some of the surface markers (e.g., CD31 and CD14) are expressed by multiple cell types and not only the cells shown here. In practice, the presence and absence of a combination of surface markers would be used to identify the cellular origin of EVs. The downstream effects of EV cargo in the context of ARDS are shown in the right panel. *The origin of EVs containing TNF-α and IL-6 mRNA is predominantly endothelial derived but may be from multiple cell types. AEC = alveolar epithelial cell; AM = alveolar macrophage; Ang-1 = angiopoetin-1; ICAM-1 = intercellular adhesion molecule-1; KC = keratinocyte-derived chemokine; KGF = keratinocyte growth factor; miR = microRNA; MSC = mesenchymal stromal cell.