Skip to main content

Lund University Publications

LUND UNIVERSITY LIBRARIES

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

Nordin, Sara LU ; Jovic, Sandra LU ; Kurut Sabanoglu, Anil LU ; Andersson, Cecilia LU ; Gela, Anele LU ; Bjartell, Anders LU ; Mörgelin, Matthias LU ; Olin, Anders LU ; Lund, Mikael LU orcid and Egesten, Arne LU (2013) In American Journal of Respiratory Cell and Molecular Biology 49(6). p.935-942
Abstract
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... (More)
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. (Less)
Please use this url to cite or link to this publication:
author
; ; ; ; ; ; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
American Journal of Respiratory Cell and Molecular Biology
volume
49
issue
6
pages
935 - 942
publisher
American Thoracic Society
external identifiers
  • wos:000328261800007
  • pmid:23815177
  • scopus:84890038611
  • pmid:23815177
ISSN
1535-4989
DOI
10.1165/rcmb.2013-0106OC
language
English
LU publication?
yes
additional info
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)
id
f5c9947c-c1e1-476b-b745-5e991330ecf2 (old id 3956309)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/23815177?dopt=Abstract
date added to LUP
2016-04-01 11:13:51
date last changed
2023-04-03 22:47:27
@article{f5c9947c-c1e1-476b-b745-5e991330ecf2,
  abstract     = {{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.}},
  author       = {{Nordin, Sara and Jovic, Sandra and Kurut Sabanoglu, Anil and Andersson, Cecilia and Gela, Anele and Bjartell, Anders and Mörgelin, Matthias and Olin, Anders and Lund, Mikael and Egesten, Arne}},
  issn         = {{1535-4989}},
  language     = {{eng}},
  number       = {{6}},
  pages        = {{935--942}},
  publisher    = {{American Thoracic Society}},
  series       = {{American Journal of Respiratory Cell and Molecular Biology}},
  title        = {{High Expression of Midkine in the Airways of Patients with Cystic Fibrosis.}},
  url          = {{http://dx.doi.org/10.1165/rcmb.2013-0106OC}},
  doi          = {{10.1165/rcmb.2013-0106OC}},
  volume       = {{49}},
  year         = {{2013}},
}