House dust mite and the integrity of the airway epithelium: mechanisms involved in the development of allergic asthma

Sijranke Post

Research output: ThesisThesis fully internal (DIV)

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The airway epithelium forms the first barrier against aeroallergens, including house dust mite (HDM), exerts pro-inflammatory activity when damaged, and is a key player in the initiation of allergic responses. Although initially it was thought that the serine proteolytic activity of HDM contributes to loss of the cell-cell contacts including E-cadherin, barrier dysfunction and pro-inflammatory reaction of the airway epithelium, we recently observed that the HDM-induced epithelial responses are independent on their serine protease activities. Additionally we investigated the role of proteaseactivated receptor-2 (PAR-2) in a HDM mouse model and found that HDM extracts that widely differed in protease activity evoked highly similar allergic reactions in Wt and PAR2 KO mice, with exception of the IgE response. Instead, our experiments have shown that HDM initiates the influx of calcium, responsible for both barrier dysfunction and secretion of the pro-inflammatory cytokine CCL20. Furthermore, we found that primary bronchial epithelial cells (PBECs) from asthmatics are more prone to develop barrier dysfunction and secretion of pro-inflammatory cytokines then healthy control PBECs in response to HDM. To test the role for loss of E-cadherin in allergic sensitization and airway remodelling, we have generated an lung-specific E-cadherin deficient mouse where E-cadherin deficiency was induced in respiratory epithelial cells during development of the respiratory epithelium using doxycycline. These mice developed spontaneously goblet cell metaplasia, inflammation and bronchial epithelial aplasia when mice reached an adult age, and will be used in future experiments for additional investigations regarding the role of E-cadherin in the development of allergic asthma.
Original languageEnglish
QualificationDoctor of Philosophy
  • Heijink, Irene, Supervisor
  • Nawijn, Martijn, Supervisor
  • van Oosterhout, Antoon, Supervisor
Award date30-Oct-2013
Place of PublicationGroningen
Print ISBNs9789036764360
Electronic ISBNs9789036766074
Publication statusPublished - 2013


  • Proefschriften (vorm)
  • Calcium
  • Receptoren
  • Cadherinen
  • Astma
  • Allergie
  • Epitheel
  • Luchtwegen (anatomie)
  • Mijten
  • Huisstofmijten
  • thorax
  • immunologische ziekten

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