Neutrophil elastase-mediated increase in airway temperature during inflammation

Annika Schmidt, Azzaq Belaaouaj, Rosi Bissinger, Garrit Koller, Laurette Malleret, Ciro D'Orazio, Martino Facchinelli, Bernhard Schulte-Hubbert, Antonio Molinaro, Otto Holst, Jutta Hammermann, Monika Schniederjans, Keith C. Meyer, Soeren Damkiaer, Giorgio Piacentini, Baroukh Assael, Kenneth Bruce, Susanne Häußler, John J LiPuma, Joachim SeeligDieter Worlitzsch, Gerd Doring

Research output: Contribution to journalArticlepeer-review

25 Citations (Scopus)

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.
Original languageEnglish
Pages (from-to)623-631
Number of pages9
JournalJournal Of Cystic Fibrosis
Volume13
Issue number6
DOIs
Publication statusPublished - Dec 2014

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