Extracellular vesicles in the pathogenesis and treatment of acute lung injury

Abstract

Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are common life-threatening lung diseases associated with acute and severe inflammation. Both have high mortality rates, and despite decades of research on clinical ALI/ARDS, there are no effective therapeutic strategies. Disruption of alveolar-capillary barrier integrity or activation of inflammatory responses leads to lung inflammation and injury. Recently, studies on the role of extracellular vesicles (EVs) in regulating normal and pathophysiologic cell activities, including inflammation and injury responses, have attracted attention. Injured and dysfunctional cells often secrete EVs into serum or bronchoalveolar lavage fluid with altered cargoes, which can be used to diagnose and predict the development of ALI/ARDS. EVs secreted by mesenchymal stem cells can also attenuate inflammatory reactions associated with cell dysfunction and injury to preserve or restore cell function, and thereby promote cell proliferation and tissue regeneration. This review focuses on the roles of EVs in the pathogenesis of pulmonary inflammation, particularly ALI/ARDS.

Targeting Receptor-Interacting Protein Kinase 1 by Novel Benzothiazole Derivatives: Treatment of Acute Lung Injury through the Necroptosis Pathway

“…10−12 Recently, some novel therapies, such as mesenchymal stem cells, targeting inflammatory storms by novel proteins, have attracted attention to reduce lung injury. 13,14 Thus, further treatments involving novel mechanisms to improve the overall survival rate are required.…”

“…Recent studies have shown that corticosteroids can reduce the mortality of ALI/ARDS in the intensive care unit (ICU) patients, but severe side effects cannot be avoided . The therapies, such as antioxidants, ketoconazole, and exogenous surfactants, exhibited promising clinical outcomes in animal models, whereas they have not realized clinical transformation. − Recently, some novel therapies, such as mesenchymal stem cells, targeting inflammatory storms by novel proteins, have attracted attention to reduce lung injury. , Thus, further treatments involving novel mechanisms to improve the overall survival rate are required.…”

Extracellular Vesicle ITGAM and ITGB2 Mediate Severe Acute Pancreatitis-Related Acute Lung Injury

“…10 Damage to this barrier that results in increased alveolar permeability is a key characteristic of ALI, as this allows water, red blood cells, pro-inflammatory factors (e.g., reactive oxygen species [ROS] and tumor necrosis factor-α [TNFα]), and immune cells (e.g., neutrophils and monocytes) to freely enter and exit the alveoli, which promotes lung inflammation and dysfunction. 7,8,11 PMVECs that line vessels of the pulmonary circulatory system maintain their integrity and act as highly impermeable barriers that prevent the free passage of water, solutes, pathogens, and immune cells between the microvessels and the lung interstitium. 11,12 PMVEC dysfunction (e.g., abnormal proliferation, apoptosis, necrosis, or tight junction disruption) can disrupt this barrier and promote the development of ALI.…”

“…g ., reactive oxygen species [ROS] and tumor necrosis factor-α [TNFα]), and immune cells ( e . g ., neutrophils and monocytes) to freely enter and exit the alveoli, which promotes lung inflammation and dysfunction. ,, PMVECs that line vessels of the pulmonary circulatory system maintain their integrity and act as highly impermeable barriers that prevent the free passage of water, solutes, pathogens, and immune cells between the microvessels and the lung interstitium. , PMVEC dysfunction ( e . g ., abnormal proliferation, apoptosis, necrosis, or tight junction disruption) can disrupt this barrier and promote the development of ALI. , Restoring PMVEC barrier integrity or preventing its disruption is thus a good means to treat ALI caused by dysregulation of endogenous cytokines ( e .…”

Therapeutic application of extracellular vesicle-encapsulated CC16 in acute lung injury

“…EVs from different sources can contain pro- or anti-inflammatory factors, regulating different kinds of alveolar cells, including epithelial cells, endothelial cells, macrophages, and neutrophils. 8 Although the characterization of sEV-CC16 is well described, the immortalized cell source is not recommended for clinical therapy. Moreover, the sEV-control did not exhibit therapeutic effects, suggesting that sEVs themselves did not act as a functional factor.…”