ABSTRACT
Acute lung injury/acute respiratory distress syndrome (ALI/ARDS) is characterised by an uncontrolled inflammatory response, and current treatment strategies have limited efficacy. Although the protective effect of M2-like macrophages (M2φ) and their extracellular vesicles (EVs) has been well-documented in other inflammatory diseases, the role of M2φ-derived EVs (M2φ-EVs) in the pathogenesis of ALI/ARDS remains poorly understood. The present study utilised a mouse model of lipopolysaccharide-induced ALI to first demonstrate a decrease in endogenous M2-like alveolar macrophage-derived EVs. And then, intratracheal instillation of exogenous M2φ-EVs from the mouse alveolar macrophage cell line (MH-S) primarily led to a take up by alveolar macrophages, resulting in reduced lung inflammation and injury. Mechanistically, the M2φ-EVs effectively suppressed the pyroptosis of alveolar macrophages and inhibited the release of excessive cytokines such as IL-6, TNF-α and IL-1ß both in vivo and in vitro, which were closely related to NF-κB/NLRP3 signalling pathway inhibition. Of note, the protective effect of M2φ-EVs was partly mediated by miR-709, as evidenced by the inhibition of miR-709 expression in M2φ-EVs mitigated their protective effect against lipopolysaccharide-induced ALI in mice. In addition, we found that the expression of miR-709 in EVs derived from bronchoalveolar lavage fluid was correlated negatively with disease severity in ARDS patients, indicating its potential as a marker for ARDS severity. Altogether, our study revealed that M2φ-EVs played a protective role in the pathogenesis of ALI/ARDS, partly mediated by miR-709, offering a potential strategy for assessing disease severity and treating ALI/ARDS.
Subject(s)
Acute Lung Injury , Extracellular Vesicles , MicroRNAs , Respiratory Distress Syndrome , Humans , Mice , Animals , Lipopolysaccharides , Extracellular Vesicles/metabolism , Acute Lung Injury/chemically induced , Acute Lung Injury/metabolism , Acute Lung Injury/pathology , Macrophages/metabolism , Respiratory Distress Syndrome/chemically induced , Respiratory Distress Syndrome/metabolism , MicroRNAs/metabolismABSTRACT
Glibenclamide displays an anti-inflammatory response in various pulmonary diseases, but its exact role in lipopolysaccharide- (LPS-) induced acute lung injury (ALI) or acute respiratory distress syndrome (ARDS) remains unknown. Herein, we aimed to explore the effect of glibenclamide in vivo and in vitro on the development of LPS-induced ALI in a mouse model. LPS stimulation resulted in increases in lung injury score, wet/dry ratio, and capillary permeability in lungs, as well as in total protein concentration, inflammatory cells, and inflammatory cytokines including IL-1ß, IL-18 in bronchoalveolar lavage fluid (BALF), and lung tissues, whereas glibenclamide treatment reduced these changes. Meanwhile, the increased proteins of NLRP3 and Caspase-1/p20 after LPS instillation in lungs were downregulated by glibenclamide. Similarly, in vitro experiments also found that glibenclamide administration inhibited the LPS-induced upregulations in cytokine secretions of IL-1ß and IL-18, as well as in the expression of components in NLRP3 inflammasome in mouse peritoneal macrophages. Of note, glibenclamide had no effect on the secretion of TNF-α in vivo nor in vitro, implicating that its anti-inflammatory effect is relatively specific to NLRP3 inflammasome. In conclusion, glibenclamide alleviates the development of LPS-induced ALI in a mouse model via inhibiting the NLRP3/Caspase-1/IL-1ß signaling pathway, which might provide a new strategy for the treatment of LPS-induced ALI.
Subject(s)
Acute Lung Injury , Inflammasomes , Acute Lung Injury/chemically induced , Acute Lung Injury/drug therapy , Acute Lung Injury/metabolism , Animals , Glyburide/pharmacology , Glyburide/therapeutic use , Inflammasomes/metabolism , Lipopolysaccharides/toxicity , Lung/metabolism , Mice , Mice, Inbred C57BL , NLR Family, Pyrin Domain-Containing 3 Protein/metabolism , Signal TransductionSubject(s)
Angiotensin-Converting Enzyme 2/biosynthesis , Antiviral Agents/pharmacology , COVID-19 Drug Treatment , Interferon Type I/pharmacology , Receptors, Virus/biosynthesis , STAT1 Transcription Factor/antagonists & inhibitors , Vidarabine/analogs & derivatives , A549 Cells , Angiotensin-Converting Enzyme 2/genetics , Binding Sites , COVID-19/enzymology , COVID-19/virology , Enzyme Induction , HEK293 Cells , HeLa Cells , Humans , Phosphorylation , Promoter Regions, Genetic , Receptors, Virus/genetics , STAT1 Transcription Factor/metabolism , Vidarabine/pharmacologyABSTRACT
Perioperative coagulopathy and bleeding are common complications in cardiovascular surgery with cardiopulmonary bypass and result in an increased rate of allogeneic blood transfusion. Both bleeding and transfusion can increase postoperative mortality and morbidity. Patient blood management can significantly reduce allogeneic blood transfusions, improve clinical outcomes, and conserve blood resources; however, measures to protect platelets from destruction by cardiopulmonary bypass still are lacking. As an unusual method of autologous blood transfusion, autologous platelet-rich plasmapheresis can effectively protect platelets from damage and has been used successfully in cardiovascular surgery. This narrative review aims to address some major clinical applications and debates of using autologous platelet-rich plasmapheresis in cardiovascular surgery. In addition, this review summarizes the application of autologous platelet gel, a product developed from autologous platelet-rich plasma, in cardiac surgery.
