Publication

DAMPs, endogenous danger signals fueling airway inflammation in COPD

Pouwels, S., 2017, [Groningen]: Rijksuniversiteit Groningen. 222 p.

Research output: ThesisThesis fully internal (DIV)

Copy link to clipboard

Documents

  • Title and contents

    Final publisher's version, 161 KB, PDF document

  • Chapter I

    Final publisher's version, 666 KB, PDF document

  • Chapter II

    Final publisher's version, 1.28 MB, PDF document

  • Chapter III

    Final publisher's version, 1.47 MB, PDF document

  • Chapter IV

    Final publisher's version, 2.04 MB, PDF document

  • Chapter V

    Final publisher's version, 3.82 MB, PDF document

  • Chapter VI

    Final publisher's version, 737 KB, PDF document

  • Chapter VII

    Final publisher's version, 3.06 MB, PDF document

  • Chapter VIII

    Final publisher's version, 1.07 MB, PDF document

  • Chapter IX

    Final publisher's version, 1.08 MB, PDF document

  • Chapter X

    Final publisher's version, 2.58 MB, PDF document

  • Chapter XI

    Final publisher's version, 3.51 MB, PDF document

  • Chapter XII

    Final publisher's version, 2.35 MB, PDF document

  • Chapter XIII

    Final publisher's version, 1.47 MB, PDF document

  • Chapter XIV

    Final publisher's version, 1.15 MB, PDF document

  • Appendix I

    Final publisher's version, 814 KB, PDF document

  • Appendix II

    Final publisher's version, 14.4 MB, PDF document

  • Complete thesis

    Final publisher's version, 27.6 MB, PDF document

  • Propositions

    Final publisher's version, 39 KB, PDF document

COPD is a severe and progressive lung disease characterized by both chronic bronchitis as well as emphysema. In the Netherlands alone every year 7,000 people die from the consequences of COPD. COPD is caused by the chronic inhalation of toxic gases, like cigarette smoke. Furthermore, genetic predisposition contributes to the risk of developing COPD. To date, the underlying molecular and cellular mechanisms of COPD are largely unknown.
In this thesis we studied the role of endogenous danger signals, called DAMPs, in COPD. We hypothesized that exposure of the lungs of genetically susceptible individuals to toxic gases induces immunogenic cell death followed by the release of DAMPs which contribute the airway inflammation in COPD patients. Here, we used both in vitro cellular models with cells isolated from COPD patients and controls as well as in vivo mouse models to show that airway epithelial cells release DAMPs upon cigarette smoke exposure and that these DAMPs have pro-inflammatory functions. Moreover, we showed that the release of specific DAMPs is increased in COPD patients. Furthermore, we have identified several novel susceptibility genes for cigarette smoke-induced airway inflammation and DAMP release. These results indicate that DAMPs play an important role in the pathophysiology of COPD.
In conclusion, this thesis shows that DAMPs are a novel possible target for future therapies of COPD patients. Future studies are needed to investigate which DAMPs or DAMP receptors show the highest therapeutic potential upon inhibition.
Original languageEnglish
QualificationDoctor of Philosophy
Awarding Institution
Supervisors/Advisors
Award date10-May-2017
Place of Publication[Groningen]
Publisher
Print ISBNs978-90-367-9766-5
Electronic ISBNs978-90-367-9765-8
Publication statusPublished - 2017

Download statistics

No data available

ID: 41518130