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Unraveling Molecular and Functional Responses Across 3 Lung Injury Models to Expand the Donor Lung Pool

Hirdman, Gabriel LU ; Stenlo, Martin LU ; Bèchet, Nicholas Burdon LU ; Niroomand, Anna LU ; Mittendorfer, Margareta LU ; Wang, Qi LU ; Edström, Dag LU ; Ghaidan, Haider LU orcid ; Kjellström, Sven LU and Pierre, Leif LU , et al. (2025) In Transplantation
Abstract

BACKGROUND: Lung transplantation remains hampered by a scarcity of viable donor lungs, partially attributed to donor lung injuries.

METHODS: Three porcine lung injury models were studied: infection-induced using lipopolysaccharide (n = 7), aspiration-induced using endotracheal gastric content (n = 7), and injury using lavage and harmful ventilation (ventilator-induced lung injury; n = 7). Molecular and functional changes from before and after the establishment of lung injury were examined with histopathology, immunohistochemistry, cytokine levels, hemodynamics, and mass spectrometric analysis of lung tissue. The respiratory tract lining fluid was analyzed using exhaled breath particles.

RESULTS: T-cell proliferation and... (More)

BACKGROUND: Lung transplantation remains hampered by a scarcity of viable donor lungs, partially attributed to donor lung injuries.

METHODS: Three porcine lung injury models were studied: infection-induced using lipopolysaccharide (n = 7), aspiration-induced using endotracheal gastric content (n = 7), and injury using lavage and harmful ventilation (ventilator-induced lung injury; n = 7). Molecular and functional changes from before and after the establishment of lung injury were examined with histopathology, immunohistochemistry, cytokine levels, hemodynamics, and mass spectrometric analysis of lung tissue. The respiratory tract lining fluid was analyzed using exhaled breath particles.

RESULTS: T-cell proliferation and suppression of complement activation were unique to the gastric injury, whereas the ventilator-induced lung injury group displayed a unique activation of monocyte chemotaxis. The lipopolysaccharide injury exhibited an activation of stress response proteins. Alterations in the extracellular matrix, particularly the degradation of collagen type IV and increased elastin expression, were identified as a consistent indicator of acute lung injury. Additionally, increases in exhaled particles and differential expression of proteins in the respiratory tract lining fluid correlated with deteriorating lung function.

CONCLUSIONS: Molecular analysis of the lung indicated distinct key differences and similarities of donor lung injury phenotypes. Analysis of various donor lung injuries suggests a heightened emphasis on the extracellular matrix for the restoration and rejuvenation of damaged donor lungs.

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organization
publishing date
type
Contribution to journal
publication status
epub
subject
in
Transplantation
pages
9 pages
publisher
Lippincott Williams & Wilkins
external identifiers
  • scopus:85218797751
  • pmid:39969856
ISSN
1534-6080
DOI
10.1097/TP.0000000000005353
language
English
LU publication?
yes
additional info
Copyright © 2025 The Author(s). Published by Wolters Kluwer Health, Inc.
id
27a7496a-8027-4919-ae4a-97697b444b66
date added to LUP
2025-02-20 14:09:20
date last changed
2025-07-22 08:28:21
@article{27a7496a-8027-4919-ae4a-97697b444b66,
  abstract     = {{<p>BACKGROUND: Lung transplantation remains hampered by a scarcity of viable donor lungs, partially attributed to donor lung injuries.</p><p>METHODS: Three porcine lung injury models were studied: infection-induced using lipopolysaccharide (n = 7), aspiration-induced using endotracheal gastric content (n = 7), and injury using lavage and harmful ventilation (ventilator-induced lung injury; n = 7). Molecular and functional changes from before and after the establishment of lung injury were examined with histopathology, immunohistochemistry, cytokine levels, hemodynamics, and mass spectrometric analysis of lung tissue. The respiratory tract lining fluid was analyzed using exhaled breath particles.</p><p>RESULTS: T-cell proliferation and suppression of complement activation were unique to the gastric injury, whereas the ventilator-induced lung injury group displayed a unique activation of monocyte chemotaxis. The lipopolysaccharide injury exhibited an activation of stress response proteins. Alterations in the extracellular matrix, particularly the degradation of collagen type IV and increased elastin expression, were identified as a consistent indicator of acute lung injury. Additionally, increases in exhaled particles and differential expression of proteins in the respiratory tract lining fluid correlated with deteriorating lung function.</p><p>CONCLUSIONS: Molecular analysis of the lung indicated distinct key differences and similarities of donor lung injury phenotypes. Analysis of various donor lung injuries suggests a heightened emphasis on the extracellular matrix for the restoration and rejuvenation of damaged donor lungs.</p>}},
  author       = {{Hirdman, Gabriel and Stenlo, Martin and Bèchet, Nicholas Burdon and Niroomand, Anna and Mittendorfer, Margareta and Wang, Qi and Edström, Dag and Ghaidan, Haider and Kjellström, Sven and Pierre, Leif and Olm, Franziska and Hyllén, Snejana and Lindstedt, Sandra}},
  issn         = {{1534-6080}},
  language     = {{eng}},
  month        = {{02}},
  publisher    = {{Lippincott Williams & Wilkins}},
  series       = {{Transplantation}},
  title        = {{Unraveling Molecular and Functional Responses Across 3 Lung Injury Models to Expand the Donor Lung Pool}},
  url          = {{http://dx.doi.org/10.1097/TP.0000000000005353}},
  doi          = {{10.1097/TP.0000000000005353}},
  year         = {{2025}},
}