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.
Highlights
Acute lung injury (ALI) is a common clinical lung disease, and can cause death, and the survivals may develop acute respiratory distress syndrome (ARDS) due to fibrotic repair of the lung
We used precursor cell markers to purify exosomes derived from macrophages, epithelia and neutrophils, since these three cell types are the major cell types that contribute to the cytokine production and secretion after ALI
The dynamics of exosome release from macrophages, epithelial cells and neutrophils within the alveolar space were determined during the different phase (1 hour, 4 hours, 8 hours, 16 hours and 32 hours) of LPS-induced ALI in mice
Summary
Acute lung injury (ALI) is a common clinical lung disease, and can cause death, and the survivals may develop acute respiratory distress syndrome (ARDS) due to fibrotic repair of the lung. Exosomes are cell-secreted nanosized bi-lipid membrane in the secretome. Bidirectional communication occurs in microenvironment via exosomes and microvesicles (MVs) [6]. Exosomes and MVs carry nucleic acids, proteins, and lipids between different cells of the tumor microenvironment, which influence a multitude of pathways biologically. Exosomes and microvesicles (MVs) are released into the extracellular environment on fusion with the plasma membrane [6]. The validation of which includes expression of CD9, CD63, CD81, ALIX and TSG101, are important mediators for cellular communication and play critical roles during macrophage differentiation, proliferation and function [7]. The exact effects of alveolar macrophage derived exosomes on ALI remain unknow
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