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Photo Mikael Lund

Mikael Lund

Professor

Photo Mikael Lund

High Expression of Midkine in the Airways of Patients with Cystic Fibrosis.

Author

  • Sara Nordin
  • Sandra Jovic
  • Anil Kurut Sabanoglu
  • Cecilia Andersson
  • Anele Gela
  • Anders Bjartell
  • Matthias Mörgelin
  • Anders Olin
  • Mikael Lund
  • Arne Egesten

Summary, in English

Mutations in the CFTR gene result in impaired host defense during cystic fibrosis (CF), where Pseudomonas aeruginosa becomes a key pathogen. We investigated the expression pattern of the antibacterial growth factor midkine in CF and possible interference with its activity by the altered airway microenvironment. High midkine expression was found in CF lung tissue compared with controls, involving epithelium of the large and small airways, alveoli, and cells of the submucosa (i.e. neutrophils and mast cells). In CF sputum, midkine was present at 100-fold higher levels but was also subject to increased degradation, compared with midkine in sputum from healthy controls. Midkine had a bactericidal effect on P. aeruginosa but increasing salt concentrations and low pH impaired the activity. Molecular modeling suggested that the effects of salt and pH were due to electrostatic screening and a charge-neutralization of the membrane, respectively. Both neutrophil elastase and elastase of P. aeruginosa cleaved midkine to smaller fragments, resulting in impaired bactericidal activity. Thus, midkine is highly expressed in CF but its bactericidal properties may be impaired by the altered microenvironment as reflected by the in vitro conditions used in this study.

Department/s

  • Respiratory Medicine, Allergology, and Palliative Medicine
  • Infection Medicine (BMC)
  • Computational Chemistry
  • Airway Inflammation and Immunology
  • Urological cancer, Malmö
  • EpiHealth: Epidemiology for Health
  • eSSENCE: The e-Science Collaboration

Publishing year

2013

Language

English

Pages

935-942

Publication/Series

American Journal of Respiratory Cell and Molecular Biology

Volume

49

Issue

6

Document type

Journal article

Publisher

American Thoracic Society

Topic

  • Cell and Molecular Biology

Status

Published

Research group

  • Airway Inflammation and Immunology
  • Urological cancer, Malmö

ISBN/ISSN/Other

  • ISSN: 1535-4989