Imperial College London
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DrKieranO'Dea

Faculty of Medicine, Department of Surgery & Cancer

Senior Lecturer in Translational Critical Care
 
 
 
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Contact

 

k.odea

 
 
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Location

 

G3.43Chelsea and Westminster HospitalChelsea and Westminster Campus

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Summary

 

Publications

Citation

BibTex format

@article{Soni:2022:10.3389/fimmu.2022.853769,
author = {Soni, S and O'Dea, K and Abe, E and Khamdan, M and Shah, S and Sarathchandra, P and Wilson, MR and Takata, M},
doi = {10.3389/fimmu.2022.853769},
journal = {Frontiers in Immunology},
title = {Microvesicle-mediated communication within the alveolar space: mechanisms of uptake by epithelial cells and alveolar macrophages},
url = {http://dx.doi.org/10.3389/fimmu.2022.853769},
volume = {13},
year = {2022}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - Intra-alveolar microvesicles (MVs) are important mediators of inter-cellular communication within the alveolar space, and are key components in the pathophysiology of lung inflammation such as acute respiratory distress syndrome (ARDS). Despite the abundance of data detailing the pro-inflammatory effects of MVs, it remains unclear how MVs interact or signal with target cells in the alveolus. Using both in vivo and in vitro alveolar models, we analyzed the dynamics of MV uptake by resident alveolar cells: alveolar macrophages and epithelial cells. Under resting conditions, the overwhelming majority of MVs were taken up by alveolar macrophages. However, following lipopolysaccharide (LPS)-mediated inflammation, epithelial cells internalized significantly more MVs (p<0.01) whilst alveolar macrophage internalization was significantly reduced (p<0.01). We found that alveolar macrophages adopted a pro-inflammatory phenotype after internalizing MVs under resting conditions, but reduction of MV uptake following LPS pre-treatment was associated with loss of inflammatory phenotype. Instead, MVs induced significant epithelial cell inflammation following LPS pre-treatment, when MV internalization was most significant. Using pharmacological inhibitors, we interrogated the mechanisms of MV internalization to identify which endocytic pathways and cell surface receptors are involved. We demonstrated that epithelial cells are exclusively dependent on the clathrin and caveolin dependent endocytotic pathway, whereas alveolar macrophage uptake may involve a significant phagocytic component. Furthermore, alveolar macrophages predominantly engulf MVs via scavenger receptors whilst, epithelial cells internalize MVs via a phosphatidylserine/integrin receptor mediated pathway (specifically alpha V beta III), which can be inhibited with phosphatidylserine-binding protein (i.e. annexin V). In summary, we have undertaken a comprehensive evaluation of MV internalization within the alveolar
AU  - Soni,S
AU  - O'Dea,K
AU  - Abe,E
AU  - Khamdan,M
AU  - Shah,S
AU  - Sarathchandra,P
AU  - Wilson,MR
AU  - Takata,M
DO  - 10.3389/fimmu.2022.853769
PY  - 2022///
SN  - 1664-3224
TI  - Microvesicle-mediated communication within the alveolar space: mechanisms of uptake by epithelial cells and alveolar macrophages
T2  - Frontiers in Immunology
UR  - http://dx.doi.org/10.3389/fimmu.2022.853769
UR  - http://hdl.handle.net/10044/1/96681
VL  - 13
ER  -
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