Skip to main content

Lund University Publications

LUND UNIVERSITY LIBRARIES

Mast Cell-Mediated Orchestration of Airway Epithelial Responses in Chronic Respiratory Diseases

Berlin, Frida LU (2023) In Lund University, Faculty of Medicine Doctoral Dissertation Series
Abstract
Chronic respiratory diseases, such as asthma, are an increasing health issue worldwide and cause about 3.9 million deaths annually. Despite this, little is know about the molecular mechanisms underpinning disease pathogenesis. Bronchial and alveolar remodeling and impaired epithelial function are typical characteristics of chronic respiratory diseases. In these patients, an increased number of mast cells, positive for the serine proteases; tryptase and chymase, infiltrate the epithelium and the alveolar
parenchyma. While it is likely that the epithelial cells are exposed to various amounts of released tryptase and chymase, the interaction between mast cells and epithelial cells remains unknown. This thesis aimed to investigate the... (More)
Chronic respiratory diseases, such as asthma, are an increasing health issue worldwide and cause about 3.9 million deaths annually. Despite this, little is know about the molecular mechanisms underpinning disease pathogenesis. Bronchial and alveolar remodeling and impaired epithelial function are typical characteristics of chronic respiratory diseases. In these patients, an increased number of mast cells, positive for the serine proteases; tryptase and chymase, infiltrate the epithelium and the alveolar
parenchyma. While it is likely that the epithelial cells are exposed to various amounts of released tryptase and chymase, the interaction between mast cells and epithelial cells remains unknown. This thesis aimed to investigate the impact of mast cell proteases on bronchial and alveolar remodelling. Human bronchial and alveolar epithelial cells were treated with tryptase and chymase. Holographic live cell imaging, fluorescent microscopy, and gene and protein assays were used to analyze various parameters such as proliferation patterns, protein expressions and distributions. The results showed that both tryptase and chymase promoted epithelial remodelling in several ways. Tryptase induced cell growth, cell survival, and wound healing, whereas chymase reduced cell growth, altered cell morphology and impaired epithelial barrier properties. In conclusion, our results suggest that intraepithelial and alveolar mast cell release of proteases plays a crucial role in epithelial homeostasis, and that an imbalance of the protease release may be involved in respiratory disease progression and in disruption of critical epithelial functions. (Less)
Please use this url to cite or link to this publication:
author
supervisor
opponent
  • docent Wernersson, Sara, Swedish University of Agricultural Science
organization
publishing date
type
Thesis
publication status
published
subject
keywords
Mast cell, Tryptase, Chymase, Bronchial epithelium, Respiratory diseases
in
Lund University, Faculty of Medicine Doctoral Dissertation Series
issue
2023:101
pages
64 pages
publisher
Lund University, Faculty of Medicine
defense location
Belfragesalen, BMC D15, Klinikgatan 32 i Lund
defense date
2023-09-07 09:15:00
ISSN
1652-8220
ISBN
978-91-8021-441-4
language
English
LU publication?
yes
id
746ce43c-aac9-46a8-9630-9687c74051bd
date added to LUP
2023-08-07 11:37:35
date last changed
2023-08-16 13:38:31
@phdthesis{746ce43c-aac9-46a8-9630-9687c74051bd,
  abstract     = {{Chronic respiratory diseases, such as asthma, are an increasing health issue worldwide and cause about 3.9 million deaths annually. Despite this, little is know about the molecular mechanisms underpinning disease pathogenesis. Bronchial and alveolar remodeling and impaired epithelial function are typical characteristics of chronic respiratory diseases. In these patients, an increased number of mast cells, positive for the serine proteases; tryptase and chymase, infiltrate the epithelium and the alveolar<br/>parenchyma. While it is likely that the epithelial cells are exposed to various amounts of released tryptase and chymase, the interaction between mast cells and epithelial cells remains unknown. This thesis aimed to investigate the impact of mast cell proteases on bronchial and alveolar remodelling. Human bronchial and alveolar epithelial cells were treated with tryptase and chymase. Holographic live cell imaging, fluorescent microscopy, and gene and protein assays were used to analyze various parameters such as proliferation patterns, protein expressions and distributions. The results showed that both tryptase and chymase promoted epithelial remodelling in several ways. Tryptase induced cell growth, cell survival, and wound healing, whereas chymase reduced cell growth, altered cell morphology and impaired epithelial barrier properties. In conclusion, our results suggest that intraepithelial and alveolar mast cell release of proteases plays a crucial role in epithelial homeostasis, and that an imbalance of the protease release may be involved in respiratory disease progression and in disruption of critical epithelial functions.}},
  author       = {{Berlin, Frida}},
  isbn         = {{978-91-8021-441-4}},
  issn         = {{1652-8220}},
  keywords     = {{Mast cell; Tryptase; Chymase; Bronchial epithelium; Respiratory diseases}},
  language     = {{eng}},
  number       = {{2023:101}},
  publisher    = {{Lund University, Faculty of Medicine}},
  school       = {{Lund University}},
  series       = {{Lund University, Faculty of Medicine Doctoral Dissertation Series}},
  title        = {{Mast Cell-Mediated Orchestration of Airway Epithelial Responses in Chronic Respiratory Diseases}},
  url          = {{https://lup.lub.lu.se/search/files/154250884/Frida_Berlin_WEBB.pdf}},
  year         = {{2023}},
}