Neutrophil elastase-mediated increase in airway temperature during inflammation

Research output: Contribution to journalResearch articleContributedpeer-review

Contributors

  • Annika Schmidt - , University Hospital Tübingen (Author)
  • Azzaq Belaaouaj - , Centre International de Recherche en Infectiologie (Author)
  • Rosi Bissinger - , University Hospital Tübingen (Author)
  • Garrit Koller - , King's College London (KCL) (Author)
  • Laurette Malleret - , Centre International de Recherche en Infectiologie (Author)
  • Ciro D'Orazio - , University of Verona (Author)
  • Martino Facchinelli - , Ospedale Policlinico (Author)
  • Bernhard Schulte-Hubbert - , Department of internal Medicine I (Author)
  • Antonio Molinaro - , Universita' di Napoli Federico II (Author)
  • Otto Holst - , Research Center Borstel - Leibniz Lung Center (Author)
  • Jutta Hammermann - , Department of Paediatrics (Author)
  • Monika Schniederjans - , Helmholtz Centre for Infection Research (Author)
  • Keith C. Meyer - , University of Wisconsin-Madison (Author)
  • Soeren Damkiaer - , Technical University of Denmark (Author)
  • Giorgio Piacentini - , Ospedale Policlinico (Author)
  • Baroukh Assael - , University of Verona (Author)
  • Kenneth Bruce - , King's College London (KCL) (Author)
  • Susanne Häußler - , Research Center Borstel - Leibniz Lung Center (Author)
  • John J. LiPuma - , University of Michigan, Ann Arbor (Author)
  • Joachim Seelig - , University of Basel (Author)
  • Dieter Worlitzsch - , Martin Luther University Halle-Wittenberg (Author)
  • Gerd Döring - , University Hospital Tübingen (Author)

Abstract

Background: How elevated temperature is generated during airway infections represents a hitherto unresolved physiological question. We hypothesized that innate immune defence mechanisms would increase luminal airway temperature during pulmonary infection. Methods: We determined the temperature in the exhaled air of cystic fibrosis (CF) patients. To further test our hypothesis, a pouch inflammatory model using neutrophil elastase-deficient mice was employed. Next, the impact of temperature changes on the dominant CF pathogen Pseudomonas aeruginosa growth was tested by plating method and RNAseq. Results: Here we show a temperature of ~38°C in neutrophil-dominated mucus plugs of chronically infected CF patients and implicate neutrophil elastase:α1-proteinase inhibitor complex formation as a relevant mechanism for the local temperature rise. Gene expression of the main pathogen in CF, P. aeruginosa, under anaerobic conditions at 38°C vs 30°C revealed increased virulence traits and characteristic cell wall changes. Conclusion: Neutrophil elastase mediates increase in airway temperature, which may contribute to P. aeruginosa selection during the course of chronic infection in CF.

Details

Original languageEnglish
Pages (from-to)623-631
Number of pages9
JournalJournal of cystic fibrosis
Volume13
Issue number6
Publication statusPublished - 1 Dec 2014
Peer-reviewedYes

External IDs

PubMed 24713593

Keywords

Keywords

  • Inflammation, Neutrophil elastase, Pseudomonas aeruginosa, Temperature