Role of extracellular vesicles in cell-cell communication and inflammation following exposure to pulmonary toxicants

Abstract

Extracellular vesicles (EVs) have emerged as key regulators of cell-cell communication during inflammatory responses to lung injury induced by diverse pulmonary toxicants including cigarette smoke, air pollutants, hyperoxia, acids, and endotoxin. Many lung cell types, including epithelial cells and endothelial cells, as well as infiltrating macrophages generate EVs. EVs appear to function by transporting cargo to recipient cells that, in most instances, promote their inflammatory activity. Biologically active cargo transported by EVs include miRNAs, cytokines/chemokines, damage-associated molecular patterns (DAMPs), tissue factor (TF)s, and caspases. Findings that EVs are taken up by target cells such as macrophages, and that this leads to increased proinflammatory functioning provide support for their role in the development of pathologies associated with toxicant exposure. Understanding the nature of EVs responding to toxic exposures and their cargo may lead to the development of novel therapeutic approaches to mitigating lung injury.

Keywords: Cigarette smoke; Epithelial cells; Inflammation; Lipopolysaccharide; Macrophages; Ozone.

Figure 1.

Cell-cell communication between lung cell types in response to pulmonary toxicants. Exposure to cigarette smoke, ozone, hyperoxia, acid, and LPS stimulates (+) or inhibits (−) the release of extracellular vesicles (EVs) from anti-inflammatory and pro-inflammatory macrophages, epithelial cells, and endothelial cells in the lung. The EVs transport cargo (e.g., proteins, miRNAs) to recipient cells thereby influencing their function through uni- and bidirectional paracrine and autocrine signaling mechanisms.