Alveolar macrophage - derived exosomes modulate severity and outcome of acute lung injury

Abstract

Severe acute lung injury (ALI) can cause death, and the survivals may develop acute respiratory distress syndrome (ARDS) due to fibrotic repair of the lung. Alveolar macrophages play a demonstrative role during the pathogenesis of ALI, and the timing and degree of differentially polarization of macrophages determine the severity of disease and outcome. Exosomes are important mediators of cellular communication and play critical roles during macrophage differentiation, proliferation and function. Nevertheless, the exact effects of alveolar macrophage-derived exosomes on ALI remain unknow. Here, we used lipopolysaccharide (LPS) to induce ALI in mice and analyzed the exosome population in bronchoalveolar lavage fluid (BALF) from macrophages, neutrophils and epithelial cells at different time points after treatment. Our data showed that macrophages were the major secretors for early secreted pro-inflammatory cytokines in the BALF-exosomes, which likely activated neutrophils to produce a variety of pro-inflammatory cytokines and IL-10. IL-10 by neutrophils in BALF-exosomes likely in turn polarized macrophages to M2c, which may be responsible for post-ALI fibrosis. Our study thus reveals a previous non-acknowledged role of BALF-exosomes as a mediator of inflammatory response and cell crosstalk during ALI.

miR‑584 and miR‑146 are candidate biomarkers for acute respiratory distress syndrome

“…The enriched CC terms were associated with the nucleus and membrane, which are key organelles for biological regulation, protein formation and secretion. As discussed above, macrophages are important in ARDS, both in terms of pro-inflammatory and anti-inflammatory activities (34). In addition, NF-κB is a key transcription factor in the regulation of the innate immune inflammatory response in activated macrophages (35).…”

Healing after COVID-19: are survivors at risk for pulmonary fibrosis?

“…They also lead to activation of macrophage populations that clear apoptotic cellular debris. However, in acute lung injury, activated macrophages may also contribute to induction of neutrophil recruitment and activation through exosome-mediated crosstalk ( 43 ). Neutrophilic infiltrate, in turn, contributes to generation of reactive oxygen species (ROS; Fig.…”

Diagnostic and Therapeutic Applications of Extracellular Vesicles in Interstitial Lung Diseases

“…Crosstalk between these cell types in the context of the injured lung microenvironment is mediated, at least in part, by EVs [ 58 ]. For instance, alveolar macrophage-, neutrophil-, and epithelial cell-derived EVs sampled from bronchoalveolar lavage fluid (BALF) mediate the acute and resolution phases of acute lung injury through the transfer of proinflammatory cytokines including TNF-α, IL-6, and IL1-β [ 59 , 60 , 61 ]. Indeed, in EVs isolated from human healthy volunteers, BALF carries MHC I and II, CD54, CD63, and the co-stimulatory molecule CD86, implicating their potential roles in immune regulation [ 62 ].…”