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Mast Cell Proteases Promote Diverse Effects on the Plasminogen Activation System and Wound Healing in A549 Alveolar Epithelial Cells

Mogren, Sofia LU ; Berlin, Frida LU ; Eskilsson, Lykke ; Van Der Burg, Nicole LU orcid ; Tufvesson, Ellen LU and Andersson, Cecilia K. LU (2022) In Cells 11(18).
Abstract

Tissue damage, epithelial alterations, and intraepithelial presence of mast cells (MCs) are characteristics of asthma pathogenesis. Increased alveolar infiltration of MC populations has also been identified as a feature of asthma and other chronic respiratory diseases. The asthma associated receptor, urokinase plasminogen activator receptor (uPAR), has been shown to regulate bronchial epithelial repair responses. However, the impact of MC tryptase and chymase on functional properties and expression of uPAR in alveolar epithelial cells have not been fully investigated. Alveolar epithelial cell migration and wound healing were investigated using holographic live cell imaging of A549 cells in a wound scratch model post stimulation with... (More)

Tissue damage, epithelial alterations, and intraepithelial presence of mast cells (MCs) are characteristics of asthma pathogenesis. Increased alveolar infiltration of MC populations has also been identified as a feature of asthma and other chronic respiratory diseases. The asthma associated receptor, urokinase plasminogen activator receptor (uPAR), has been shown to regulate bronchial epithelial repair responses. However, the impact of MC tryptase and chymase on functional properties and expression of uPAR in alveolar epithelial cells have not been fully investigated. Alveolar epithelial cell migration and wound healing were investigated using holographic live cell imaging of A549 cells in a wound scratch model post stimulation with tryptase or chymase. The expression of uPAR was investigated on the protein and gene level from cellular supernatants and in bronchoalveolar lavage fluid fractions from allergic asthmatics. We found that tryptase improved wound healing capacity, cellular migration and membrane bound uPAR expression. Chymase reduced gap closure capacity, cellular migration and membrane bound uPAR expression but increased soluble uPAR release. Our data suggest a dual regulatory response from the MC proteases in events related to uPAR expression and wound healing which could be important features in asthmatic disease.

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author
; ; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
alveolar epithelial cells, chymase, mast cell, migration, tryptase, urokinase plasminogen activator receptor, wound healing
in
Cells
volume
11
issue
18
article number
2916
publisher
MDPI AG
external identifiers
  • pmid:36139491
  • scopus:85138665769
ISSN
2073-4409
DOI
10.3390/cells11182916
language
English
LU publication?
yes
id
87a5dd9d-e71e-4243-bcf7-d9710f6c2997
date added to LUP
2022-12-12 11:40:32
date last changed
2024-05-16 19:49:40
@article{87a5dd9d-e71e-4243-bcf7-d9710f6c2997,
  abstract     = {{<p>Tissue damage, epithelial alterations, and intraepithelial presence of mast cells (MCs) are characteristics of asthma pathogenesis. Increased alveolar infiltration of MC populations has also been identified as a feature of asthma and other chronic respiratory diseases. The asthma associated receptor, urokinase plasminogen activator receptor (uPAR), has been shown to regulate bronchial epithelial repair responses. However, the impact of MC tryptase and chymase on functional properties and expression of uPAR in alveolar epithelial cells have not been fully investigated. Alveolar epithelial cell migration and wound healing were investigated using holographic live cell imaging of A549 cells in a wound scratch model post stimulation with tryptase or chymase. The expression of uPAR was investigated on the protein and gene level from cellular supernatants and in bronchoalveolar lavage fluid fractions from allergic asthmatics. We found that tryptase improved wound healing capacity, cellular migration and membrane bound uPAR expression. Chymase reduced gap closure capacity, cellular migration and membrane bound uPAR expression but increased soluble uPAR release. Our data suggest a dual regulatory response from the MC proteases in events related to uPAR expression and wound healing which could be important features in asthmatic disease.</p>}},
  author       = {{Mogren, Sofia and Berlin, Frida and Eskilsson, Lykke and Van Der Burg, Nicole and Tufvesson, Ellen and Andersson, Cecilia K.}},
  issn         = {{2073-4409}},
  keywords     = {{alveolar epithelial cells; chymase; mast cell; migration; tryptase; urokinase plasminogen activator receptor; wound healing}},
  language     = {{eng}},
  number       = {{18}},
  publisher    = {{MDPI AG}},
  series       = {{Cells}},
  title        = {{Mast Cell Proteases Promote Diverse Effects on the Plasminogen Activation System and Wound Healing in A549 Alveolar Epithelial Cells}},
  url          = {{http://dx.doi.org/10.3390/cells11182916}},
  doi          = {{10.3390/cells11182916}},
  volume       = {{11}},
  year         = {{2022}},
}