A Heterogenous Population of Extracellular Vesicles Mobilize to the Alveoli Post-Injury.
Journal
The journal of trauma and acute care surgery
ISSN: 2163-0763
Titre abrégé: J Trauma Acute Care Surg
Pays: United States
ID NLM: 101570622
Informations de publication
Date de publication:
26 Oct 2023
26 Oct 2023
Historique:
pubmed:
26
10
2023
medline:
26
10
2023
entrez:
26
10
2023
Statut:
aheadofprint
Résumé
Acute lung injury (ALI) and subsequent resolution following severe injury are coordinated by a complex lung microenvironment that includes extracellular vesicles (EVs). We hypothesized that there is a heterogenous population of EVs recruited to the alveoli post-injury and that we could identify specific immune-relevant mediators expressed on BAL EVs as candidate biomarkers of injury and injury resolution. Mice underwent 30% TBSA burn injury and BAL fluid was collected 4 hours post-injury and compared to sham. EVs were purified and single vesicle flow cytometry (vFC) was performed using fluorescent antibodies to quantify the expression of specific cell surface markers on individual EVs. Next, we evaluated human BAL specimens from injured patients to establish translational relevance of the mouse vFC analysis. Human BAL was collected from intubated patients following trauma or burn injury, EVs were purified, then subjected to vFC analysis. A diverse population of EVs were mobilized to the alveoli after burn injury in mice. Quantitative BAL vFC identified significant increases in macrophage-derived CD44+ EVs (pre-10.8% vs. post-injury 13%, p < 0.05) and decreases in IL-6 receptor alpha (CD126) EVs (pre-19.3% vs. post-injury 9.3%, p < 0.05). BAL from injured patients also contained a heterogeneous population of EVs derived from myeloid cells, endothelium, and epithelium sources, with CD44+ EVs being highly detected. Injury causes mobilization of a heterogeneous population of EVs to the alveoli in both animal models and injured patients. Defining EV release after injury will be critical in identifying diagnostic and therapeutic targets to limit post-injury ALI. IV, Original Research.
Sections du résumé
BACKGROUND
BACKGROUND
Acute lung injury (ALI) and subsequent resolution following severe injury are coordinated by a complex lung microenvironment that includes extracellular vesicles (EVs). We hypothesized that there is a heterogenous population of EVs recruited to the alveoli post-injury and that we could identify specific immune-relevant mediators expressed on BAL EVs as candidate biomarkers of injury and injury resolution.
METHODS
METHODS
Mice underwent 30% TBSA burn injury and BAL fluid was collected 4 hours post-injury and compared to sham. EVs were purified and single vesicle flow cytometry (vFC) was performed using fluorescent antibodies to quantify the expression of specific cell surface markers on individual EVs. Next, we evaluated human BAL specimens from injured patients to establish translational relevance of the mouse vFC analysis. Human BAL was collected from intubated patients following trauma or burn injury, EVs were purified, then subjected to vFC analysis.
RESULTS
RESULTS
A diverse population of EVs were mobilized to the alveoli after burn injury in mice. Quantitative BAL vFC identified significant increases in macrophage-derived CD44+ EVs (pre-10.8% vs. post-injury 13%, p < 0.05) and decreases in IL-6 receptor alpha (CD126) EVs (pre-19.3% vs. post-injury 9.3%, p < 0.05). BAL from injured patients also contained a heterogeneous population of EVs derived from myeloid cells, endothelium, and epithelium sources, with CD44+ EVs being highly detected.
CONCLUSION
CONCLUSIONS
Injury causes mobilization of a heterogeneous population of EVs to the alveoli in both animal models and injured patients. Defining EV release after injury will be critical in identifying diagnostic and therapeutic targets to limit post-injury ALI.
LEVEL OF EVIDENCE
METHODS
IV, Original Research.
Identifiants
pubmed: 37880828
doi: 10.1097/TA.0000000000004176
pii: 01586154-990000000-00539
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Informations de copyright
Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.
Déclaration de conflit d'intérêts
Conflict of Interest Statement: The authors report no conflicts of interest relevant to this work. All JTACS Disclosure forms have been supplied to the journal and are provided as supplemental digital content ( http://links.lww.com/TA/D344 ).