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Crosstalk between mast cells and lung fibroblasts is modified by alveolar extracellular matrix and influences epithelial migration

Bagher, Mariam LU ; Rosmark, Oskar LU orcid ; Rendin, Linda Elowsson LU ; Nybom, Annika LU ; Wasserstrom, Sebastian LU ; Müller, Catharina LU ; Zhou, Xiao Hong ; Dellgren, Göran ; Hallgren, Oskar LU and Bjermer, Leif LU , et al. (2021) In International Journal of Molecular Sciences 22(2).
Abstract

Mast cells play an important role in asthma, however, the interactions between mast cells, fibroblasts and epithelial cells in idiopathic pulmonary fibrosis (IPF) are less known. The objectives were to investigate the effect of mast cells on fibroblast activity and migration of epithelial cells. Lung fibroblasts from IPF patients and healthy individuals were co-cultured with LAD2 mast cells or stimulated with the proteases tryptase and chymase. Human lung fibroblasts and mast cells were cultured on cell culture plastic plates or decellularized human lung tissue (scaffolds) to create a more physiological milieu by providing an alveolar extracellular matrix. Released mediators were analyzed and evaluated for effects on epithelial cell... (More)

Mast cells play an important role in asthma, however, the interactions between mast cells, fibroblasts and epithelial cells in idiopathic pulmonary fibrosis (IPF) are less known. The objectives were to investigate the effect of mast cells on fibroblast activity and migration of epithelial cells. Lung fibroblasts from IPF patients and healthy individuals were co-cultured with LAD2 mast cells or stimulated with the proteases tryptase and chymase. Human lung fibroblasts and mast cells were cultured on cell culture plastic plates or decellularized human lung tissue (scaffolds) to create a more physiological milieu by providing an alveolar extracellular matrix. Released mediators were analyzed and evaluated for effects on epithelial cell migration. Tryptase increased vascular endothelial growth factor (VEGF) release from fibroblasts, whereas co-culture with mast cells increased IL-6 and hepatocyte growth factor (HGF). Culture in scaffolds increased the release of VEGF compared to culture on plastic. Migration of epithelial cells was reduced by IL-6, while HGF and conditioned media from scaffold cultures promoted migration. In conclusion, mast cells and tryptase increased fibroblast release of mediators that influenced epithelial migration. These data indicate a role of mast cells and tryptase in the interplay between fibroblasts, epithelial cells and the alveolar extracellular matrix in health and lung disease.

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organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Epithelial cells, Extracellular matrix, Hepatocyte growth factor, Idiopathic pulmonary fibrosis, IL-6, Lung fibroblasts, Mast cells, Tryptase, Vascular endothelial growth factor
in
International Journal of Molecular Sciences
volume
22
issue
2
article number
506
pages
16 pages
publisher
MDPI AG
external identifiers
  • pmid:33419174
  • scopus:85099168526
ISSN
1661-6596
DOI
10.3390/ijms22020506
language
English
LU publication?
yes
id
8eff77a3-27e1-4d2f-94a5-75db2d86c106
date added to LUP
2021-01-19 13:33:22
date last changed
2025-03-21 10:04:14
@article{8eff77a3-27e1-4d2f-94a5-75db2d86c106,
  abstract     = {{<p>Mast cells play an important role in asthma, however, the interactions between mast cells, fibroblasts and epithelial cells in idiopathic pulmonary fibrosis (IPF) are less known. The objectives were to investigate the effect of mast cells on fibroblast activity and migration of epithelial cells. Lung fibroblasts from IPF patients and healthy individuals were co-cultured with LAD2 mast cells or stimulated with the proteases tryptase and chymase. Human lung fibroblasts and mast cells were cultured on cell culture plastic plates or decellularized human lung tissue (scaffolds) to create a more physiological milieu by providing an alveolar extracellular matrix. Released mediators were analyzed and evaluated for effects on epithelial cell migration. Tryptase increased vascular endothelial growth factor (VEGF) release from fibroblasts, whereas co-culture with mast cells increased IL-6 and hepatocyte growth factor (HGF). Culture in scaffolds increased the release of VEGF compared to culture on plastic. Migration of epithelial cells was reduced by IL-6, while HGF and conditioned media from scaffold cultures promoted migration. In conclusion, mast cells and tryptase increased fibroblast release of mediators that influenced epithelial migration. These data indicate a role of mast cells and tryptase in the interplay between fibroblasts, epithelial cells and the alveolar extracellular matrix in health and lung disease.</p>}},
  author       = {{Bagher, Mariam and Rosmark, Oskar and Rendin, Linda Elowsson and Nybom, Annika and Wasserstrom, Sebastian and Müller, Catharina and Zhou, Xiao Hong and Dellgren, Göran and Hallgren, Oskar and Bjermer, Leif and Larsson-Callerfelt, Anna Karin and Westergren-Thorsson, Gunilla}},
  issn         = {{1661-6596}},
  keywords     = {{Epithelial cells; Extracellular matrix; Hepatocyte growth factor; Idiopathic pulmonary fibrosis; IL-6; Lung fibroblasts; Mast cells; Tryptase; Vascular endothelial growth factor}},
  language     = {{eng}},
  number       = {{2}},
  publisher    = {{MDPI AG}},
  series       = {{International Journal of Molecular Sciences}},
  title        = {{Crosstalk between mast cells and lung fibroblasts is modified by alveolar extracellular matrix and influences epithelial migration}},
  url          = {{http://dx.doi.org/10.3390/ijms22020506}},
  doi          = {{10.3390/ijms22020506}},
  volume       = {{22}},
  year         = {{2021}},
}