Lung epithelial cell-derived extracellular vesicles activate macrophage-mediated inflammatory responses via ROCK1 pathway

Moon, Hyung‐Geun; Cao, Yuan; Yang, Jincheng; Lee, J. H.; Choi, Hye Sook; Jin, Yang

doi:10.1038/cddis.2015.282

Cited by 138 publications

(149 citation statements)

References 42 publications

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“…Depending on the cellular sources and stimuli, EVs are generated via direct budding (MVs), secretion from cells via multivesicular bodies (MVBs, Exos) or formation by plasma membrane blebbing after undergoing apoptosis (ABs). Proteins derived from parent cells are often detectable in EVs such as surfactant proteins (SPs) that can be found in EVs released from lung epithelial cells (26). We previously reported that development of hyperoxia-induced lung injury (HALI) is influenced by BALF EVs from lung epithelium (9, 26).…”

Section: Discussionmentioning

confidence: 99%

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Lung Epithelial Cell–Derived Microvesicles Regulate Macrophage Migration via MicroRNA-17/221–Induced Integrin β1 Recycling

Lee

Zhang

et al. 2017

The Journal of Immunology

106

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Robust lung inflammation is one of the prominent features in the pathogenesis of acute lung injury (ALI). Macrophage migration and recruitment are often seen at the early stage of lung inflammatory responses in response to noxious stimuli. Using an acid-inhalation induced lung injury model, we explored the mechanisms by which acid exposure initiates macrophage recruitment and migration during development of ALI. The lung epithelium comprises a large surface area and functions as a first-line defense against noxious insults. We found that acid exposure induced a remarkable microvesicle (MV) release from lung epithelium as detected in bronchoalveolar lavage fluid (BALF). Significantly elevated RNA, rather than protein, was found in these epithelium-derived MVs after acid and included several highly elevated microRNAs (miRNAs) including miR-17 and miR-221. Acid-induced-epithelial MV release promoted macrophage migration in vitro and recruitment into the lung in vivo and required, in part, MV-shuttling of miR-17 and/or miR-221. Mechanistically, acid-induced epithelial MV-miR-17/221 promoted β1 integrin recycling and presentation back onto the surface of macrophages, in part via a Rab11-mediated pathway. Integrin β1 is known to play an essential role in regulating macrophage migration. Taken together, acid-induced ALI results in epithelial MV-shuttling of miR-17/221 that in turn modulates macrophage β1 integrin recycling promoting macrophage recruitment and ultimately contribute to lung inflammation.

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Section: Discussionmentioning

confidence: 99%

“…Macrophages present at barrier sites like the lung are surveillance cells (25, 26). How macrophages migrate and are recruited from the peripheral circulation into the lung in response to a noxious stumuli remains largely unclear and is a complex process involving diverse cellular regulatory mechanisms (27–30),…”

Section: Introductionmentioning

confidence: 99%

Lung Epithelial Cell–Derived Microvesicles Regulate Macrophage Migration via MicroRNA-17/221–Induced Integrin β1 Recycling

Lee

Zhang

et al. 2017

The Journal of Immunology

106

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“…This observation suggests that in additional to being a messenger, EVs also serve as a cargo for “trash” disposal. Moreover, Moon et al further observed that epithelial EVs trigger alveolar macrophage activation and pro-inflammatory cytokine releases, confirming their roles in mediating cell-cell cross-talk [28]. …”

Section: Role Of Evs In Acute Lung Injury (Ali)mentioning

confidence: 91%

“…These compositions are derived based on the parent cells [27]. For example, lung surfactant proteins (SPs) have been detected in the EVs derived from lung epithelial cells [28]. These cell-specific proteins can serve as markers to reflect the origins of the EVs.…”

Section: Ev Compositionmentioning

confidence: 99%

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Extracellular Vesicles Facilitate the Intercellular Communications in the Pathogenesis of Lung Injury

et al. 2016

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Extracellular vesicles (EVs) are a group of heterogeneous, nano-sized structures surrounded by lipid bilayer membranes that are released by cells. Depending on their size and mechanisms of formation, EVs are often referred to as exosomes, microvesicles (MVs) and apoptotic bodies (AB). EVs are evolutionally conserved vesicles that mediate intercellular communications and cross-talk, via transferring proteins, lipids and nucleic acids. Accumulating evidence suggests that EVs exert essential physiological and pathological functions on both their mother and recipient cells. Therefore, growing interests focus on the potentials of EVs to serve as novel targets for the development of therapeutic and diagnostic strategies. Currently, extensive reports are yielded from cancer research. However, besides malignancy, EVs may also serve as crucial regulators in other devastating conditions, such as the acute respiratory distress syndrome (ARDS) and acute lung injury (ALI). The generation, regulation and function of EVs in ARDS/ALI are largely unexplored. In this mini review, we will briefly review the current understanding of EVs and their known physiological/pathological functions in the pathogenesis of ARDS/ALI. Previously, only scattered reports have been published in this field. We believe that further investigations focusing on EVs and their compositions will shed light on novel insights in the research of ARDS/ALI.

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Small Extracellular Vesicles Propagate the Inflammatory Response After Trauma

et al. 2021

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Trauma is the leading cause of death in individuals under 44 years of age. Thorax trauma (TxT) is strongly associated with trauma‐related death, an unbalanced innate immune response, sepsis, acute respiratory distress syndrome, and multiple organ dysfunction. It is shown that different in vivo traumata, such as TxT or an in vitro polytrauma cytokine cocktail trigger secretion of small extracellular nanovesicles (sEVs) from endothelial cells with pro‐inflammatory cargo. These sEVs transfer transcripts for ICAM‐1, VCAM‐1, E‐selectin, and cytokines to systemically activate the endothelium, facilitate neutrophil‐endothelium interactions, and destabilize barrier integrity. Inhibition of sEV‐release after TxT in mice ameliorates local as well as systemic inflammation, neutrophil infiltration, and distant organ damage in kidneys (acute kidney injury, AKI). Vice versa, injection of TxT‐plasma‐sEVs into healthy animals is sufficient to trigger pulmonary and systemic inflammation as well as AKI. Accordingly, increased sEV concentrations and transfer of similar cargos are observed in polytrauma patients, suggesting a fundamental pathophysiological mechanism.

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Lung epithelial cell-derived extracellular vesicles activate macrophage-mediated inflammatory responses via ROCK1 pathway

Cited by 138 publications

References 42 publications

Lung Epithelial Cell–Derived Microvesicles Regulate Macrophage Migration via MicroRNA-17/221–Induced Integrin β1 Recycling

Lung Epithelial Cell–Derived Microvesicles Regulate Macrophage Migration via MicroRNA-17/221–Induced Integrin β1 Recycling

Extracellular Vesicles Facilitate the Intercellular Communications in the Pathogenesis of Lung Injury

Small Extracellular Vesicles Propagate the Inflammatory Response After Trauma

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