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

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

Research output: Contribution to journalArticlepeer-review


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.
Original languageEnglish
Pages (from-to)935-942
JournalAmerican Journal of Respiratory Cell and Molecular Biology
Issue number6
Publication statusPublished - 2013

Bibliographical note

The information about affiliations in this record was updated in December 2015.
The record was previously connected to the following departments: Airway Inflammation and Immunology (013212038), Respiratory Medicine and Allergology (013230111), Division of Infection Medicine (BMC) (013024020), Division of Urological Cancers (013243420), Theoretical Chemistry (S) (011001039)

Subject classification (UKÄ)

  • Cell and Molecular Biology


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