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Protein signatures of remodeled airways in transplanted lungs with Bronchiolitis Obliterans Syndrome obtained using laser capture microdissection

Müller, Catharina LU ; Rosmark, Oskar LU orcid ; Åhrman, Emma LU ; Brunnström, Hans LU orcid ; Wassilew, Katharina ; Nybom, Annika LU ; Michaliková, Barbora LU ; Larsson, Hillevi LU ; Eriksson, Leif T LU and Schultz, Hans Henrik , et al. (2021) In American Journal of Pathology 191(8). p.1398-1411
Abstract

Bronchiolitis obliterans syndrome (BOS), a common form of chronic lung allograft dysfunction, is the major limitation to long-term survival after lung transplantation. The histological correlate is progressive, fibrotic occlusion of small airways, obliterative bronchiolitis lesions, ultimately leading to organ failure. The molecular composition of these lesions is unknown. By laser-capture microdissection and optimized sample preparation protocols for mass spectrometry the protein composition of the lesions in explanted lungs from four end-stage BOS patients were analysed. Immunohistochemistry and immunofluorescence were used to determine the spatial distribution of commonly identified proteins on the tissue level, protein signatures... (More)

Bronchiolitis obliterans syndrome (BOS), a common form of chronic lung allograft dysfunction, is the major limitation to long-term survival after lung transplantation. The histological correlate is progressive, fibrotic occlusion of small airways, obliterative bronchiolitis lesions, ultimately leading to organ failure. The molecular composition of these lesions is unknown. By laser-capture microdissection and optimized sample preparation protocols for mass spectrometry the protein composition of the lesions in explanted lungs from four end-stage BOS patients were analysed. Immunohistochemistry and immunofluorescence were used to determine the spatial distribution of commonly identified proteins on the tissue level, protein signatures for in total 14 OB-lesions were established. A set of 39 proteins identified in more than 75% of lesions included distinct structural proteins (collagen type IV and VI) and cellular components (actins, vimentin, tryptase). Each respective lesion exhibited a unique composition of proteins (on average n=66 proteins), thereby mirroring the morphological variation of the lesions. Antibody-based staining confirmed these MS-based findings. The 14 analyzed OB-lesions showed variations in their protein content, but also common features. This study provides molecular and morphological insights into the development of chronic rejection after lung transplantation. The protein patterns in the lesions were correlated to pathways of extracellular matrix organization, tissue development and wound healing processes.

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organization
publishing date
type
Contribution to journal
publication status
published
subject
in
American Journal of Pathology
volume
191
issue
8
pages
14 pages
publisher
American Society for Investigative Pathology
external identifiers
  • pmid:34111430
  • scopus:85110419210
ISSN
1525-2191
DOI
10.1016/j.ajpath.2021.05.014
language
English
LU publication?
yes
id
4e217fb1-c828-4169-ae7e-9cff7d01adb4
date added to LUP
2021-06-13 21:41:01
date last changed
2024-06-15 12:32:16
@article{4e217fb1-c828-4169-ae7e-9cff7d01adb4,
  abstract     = {{<p>Bronchiolitis obliterans syndrome (BOS), a common form of chronic lung allograft dysfunction, is the major limitation to long-term survival after lung transplantation. The histological correlate is progressive, fibrotic occlusion of small airways, obliterative bronchiolitis lesions, ultimately leading to organ failure. The molecular composition of these lesions is unknown. By laser-capture microdissection and optimized sample preparation protocols for mass spectrometry the protein composition of the lesions in explanted lungs from four end-stage BOS patients were analysed. Immunohistochemistry and immunofluorescence were used to determine the spatial distribution of commonly identified proteins on the tissue level, protein signatures for in total 14 OB-lesions were established. A set of 39 proteins identified in more than 75% of lesions included distinct structural proteins (collagen type IV and VI) and cellular components (actins, vimentin, tryptase). Each respective lesion exhibited a unique composition of proteins (on average n=66 proteins), thereby mirroring the morphological variation of the lesions. Antibody-based staining confirmed these MS-based findings. The 14 analyzed OB-lesions showed variations in their protein content, but also common features. This study provides molecular and morphological insights into the development of chronic rejection after lung transplantation. The protein patterns in the lesions were correlated to pathways of extracellular matrix organization, tissue development and wound healing processes.</p>}},
  author       = {{Müller, Catharina and Rosmark, Oskar and Åhrman, Emma and Brunnström, Hans and Wassilew, Katharina and Nybom, Annika and Michaliková, Barbora and Larsson, Hillevi and Eriksson, Leif T and Schultz, Hans Henrik and Perch, Michael and Malmström, Johan and Wigén, Jenny and Iversen, Martin and Westergren-Thorsson, Gunilla}},
  issn         = {{1525-2191}},
  language     = {{eng}},
  month        = {{08}},
  number       = {{8}},
  pages        = {{1398--1411}},
  publisher    = {{American Society for Investigative Pathology}},
  series       = {{American Journal of Pathology}},
  title        = {{Protein signatures of remodeled airways in transplanted lungs with Bronchiolitis Obliterans Syndrome obtained using laser capture microdissection}},
  url          = {{http://dx.doi.org/10.1016/j.ajpath.2021.05.014}},
  doi          = {{10.1016/j.ajpath.2021.05.014}},
  volume       = {{191}},
  year         = {{2021}},
}