期刊
JOURNAL OF INNATE IMMUNITY
卷 -, 期 -, 页码 -出版社
KARGER
DOI: 10.1159/000522338
关键词
Acute lung injury; Inflammation; Extracellular vesicles; Polyunsaturated fatty acids; Macrophage
类别
资金
- American Heart Association [17SDG33410982]
- National Institutes of Health [HL137224, S10RR027926]
- National Center for Research Resources [P30 CA016058, S10 OD018056]
- National Cancer Institute, Bethesda, MD, USA
- NIH
This study reveals the presence of diverse lipid mediators in extracellular vesicles (EVs) during acute lung injury (ALI), which are correlated with the inflammatory status of lung macrophages. These EVs modulate the function of macrophages and alveolar epithelial cells during ALI.
Emerging data support the pivotal role of extracellular vesicles (EVs) in normal cellular physiology and disease conditions. However, despite their abundance, there is much less information about the lipid mediators carried in EVs, especially in the context of acute lung injury (ALI). Our data demonstrate that C57BL/6 mice subjected to intranasal Escherichia coli lipopolysaccharide (LPS)-induced ALI release, a higher number of EVs into the alveolar space, compared to saline-treated controls. EVs released during ALI originated from alveolar epithelial cells, macrophages, and neutrophils and carry a diverse array of lipid mediators derived from omega-3 and omega-6 polyunsaturated fatty acids (PUFA). The eicosanoids in EVs correlated with cellular levels of arachidonic acid, expression of cytosolic phospholipase A2, cyclooxygenase (COX), lipoxygenase (LOX), and cytochrome epoxygenase p450 proteins in pulmonary macrophages. Furthermore, EVs from LPS-toll-like receptor 4 knockout (TLR4(-/-)) mice contained significantly lower amounts of COX and LOX catalyzed eicosanoids and omega-3 PUFA metabolites. More importantly, EVs from LPS-treated wild-type mice increased TNF-alpha release by macrophages and reduced alveolar epithelial monolayer barrier integrity compared to EVs from LPS-treated TLR4(-/-) mice. In summary, our study demonstrates for the first time that the EV carried PUFA metabolite profile in part depends on the inflammatory status of the lung macrophages and modulates pulmonary macrophage and alveolar epithelial cell function during LPS-induced ALI.
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