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

Research output: Contribution to journalArticle

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 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.

Details

Authors
Organisations
External organisations
  • Skåne University Hospital
  • AstraZeneca, Sweden
  • Sahlgrenska University Hospital
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Cell and Molecular Biology
  • Respiratory Medicine and Allergy

Keywords

  • Epithelial cells, Extracellular matrix, Hepatocyte growth factor, Idiopathic pulmonary fibrosis, IL-6, Lung fibroblasts, Mast cells, Tryptase, Vascular endothelial growth factor
Original languageEnglish
Article number506
Number of pages16
JournalInternational Journal of Molecular Sciences
Volume22
Issue number2
Publication statusPublished - 2021
Publication categoryResearch
Peer-reviewedYes