Tan, Ying Ying;
O'Dea, Kieran P;
Tsiridou, Diianeira Maria;
Pac Soo, Aurelie;
Koh, Marissa W;
Beckett, Florence;
Takata, Masao;
(2023)
Circulating Myeloid Cell–derived Extracellular Vesicles as Mediators of Indirect Acute Lung Injury.
American Journal of Respiratory Cell and Molecular Biology
, 68
(2)
pp. 140-149.
10.1165/rcmb.2022-0207OC.
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Abstract
Blood-borne myeloid cells, neutrophils and monocytes, play a central role in the development of indirect acute lung injury (ALI) during sepsis and noninfectious systemic inflammatory response syndrome. By contrast, the contribution of circulating myeloid cell–derived extracellular vesicles (EVs) to ALI is unknown, despite acute increases in their numbers during sepsis and systemic inflammatory response syndrome. Here, we investigated the direct role of circulating myeloid-EVs in ALI using a mouse isolated perfused lung system and a human cell coculture model of pulmonary vascular inflammation consisting of lung microvascular endothelial cells and peripheral blood mononuclear cells. Total and immunoaffinity-isolated myeloid (CD11b+) and platelet (CD41+) EVs were prepared from the plasma of intravenous LPS-injected endotoxemic donor mice and transferred directly into recipient lungs. Two-hour perfusion of lungs with unfractionated EVs from a single donor induced pulmonary edema formation and increased perfusate concentrations of RAGE (receptor for advanced glycation end products), consistent with lung injury. These responses were abolished in the lungs of monocyte-depleted mice. The isolated myeloid- but not platelet-EVs produced a similar injury response and the acute intravascular release of proinflammatory cytokines and endothelial injury markers. In the in vitro human coculture model, human myeloid- (CD11b+) but not platelet- (CD61+) EVs isolated from LPS-stimulated whole blood induced acute proinflammatory cytokine production and endothelial activation. These findings implicate circulating myeloid-EVs as acute mediators of pulmonary vascular inflammation and edema, suggesting an alternative therapeutic target for attenuation of indirect ALI.
| Type: | Article |
|---|---|
| Title: | Circulating Myeloid Cell–derived Extracellular Vesicles as Mediators of Indirect Acute Lung Injury |
| Location: | United States |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1165/rcmb.2022-0207OC |
| Publisher version: | https://doi.org/10.1165/rcmb.2022-0207OC |
| Language: | English |
| Additional information: | This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions. |
| Keywords: | Acute lung injury, Extracellular vesicles, monocytes, neutrophils, sepsis |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Infection and Immunity |
| URI: | https://discovery-pp.ucl.ac.uk/id/eprint/10161702 |
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