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Expression of MIG/CXCL9 in Cystic Fibrosis and Modulation of Its Activities by Elastase of Pseudomonas aeruginosa.

Jovic, Sandra LU ; Shikhagaie, Medya LU ; Mörgelin, Matthias LU ; Kjellström, Sven; Erjefält, Jonas LU ; Olin, Anders LU ; Frick, Inga-Maria LU and Egesten, Arne LU (2014) In Journal of Innate Immunity 6(6). p.846-859
Abstract
In cystic fibrosis (CF), colonization of the airways with Pseudomonas aeruginosa is associated with disease deterioration. The mechanism behind the disease progression is not fully understood. The present work shows that the antibacterial chemokine MIG/CXCL9 is present in the airways and in sputum of CF patients. MIG/CXCL9 showed high bactericidal activity against. P. aeruginosa, including some strains from the airways of CF patients. Full-length MIG/CXCL9 was detected in sputum from healthy controls and CF patients colonized with P. aeruginosa. However, degraded MIG/CXCL9 was only found in CF sputum. In vitro, elastase of P. aeruginosa cleaved off a fragment of similar size and two additional fragments from MIG/CXCL9. The fragments showed... (More)
In cystic fibrosis (CF), colonization of the airways with Pseudomonas aeruginosa is associated with disease deterioration. The mechanism behind the disease progression is not fully understood. The present work shows that the antibacterial chemokine MIG/CXCL9 is present in the airways and in sputum of CF patients. MIG/CXCL9 showed high bactericidal activity against. P. aeruginosa, including some strains from the airways of CF patients. Full-length MIG/CXCL9 was detected in sputum from healthy controls and CF patients colonized with P. aeruginosa. However, degraded MIG/CXCL9 was only found in CF sputum. In vitro, elastase of P. aeruginosa cleaved off a fragment of similar size and two additional fragments from MIG/CXCL9. The fragments showed less bactericidal activity against P. aeruginosa compared with the full-length protein. The fragments did not activate the MIG/CXCL9 receptor CXCR3 (expressed e.g. by NK cells, mast cells, and activated T cells) but instead displayed noncompetitive inhibition. In vitro, a decrease in CXCR3-bearing cells was found within and in the proximity of the bronchial epithelium of CF lung tissue compared with controls. Taken together, both bactericidal and cell-recruiting activities of MIG/CXCL9 are corrupted by P. aeruginosa through release of elastase, and this may contribute to impaired airway host defense in CF. © 2014 S. Karger AG, Basel. (Less)
Please use this url to cite or link to this publication:
author
organization
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type
Contribution to journal
publication status
published
subject
in
Journal of Innate Immunity
volume
6
issue
6
pages
846 - 859
publisher
Karger
external identifiers
  • pmid:25115612
  • wos:000343642800012
  • scopus:84908610311
ISSN
1662-811X
DOI
10.1159/000365399
language
English
LU publication?
yes
id
c14b216c-cde2-4251-a923-eef457d67895 (old id 4614894)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/25115612?dopt=Abstract
date added to LUP
2014-09-06 22:43:05
date last changed
2017-03-26 03:19:57
@article{c14b216c-cde2-4251-a923-eef457d67895,
  abstract     = {In cystic fibrosis (CF), colonization of the airways with Pseudomonas aeruginosa is associated with disease deterioration. The mechanism behind the disease progression is not fully understood. The present work shows that the antibacterial chemokine MIG/CXCL9 is present in the airways and in sputum of CF patients. MIG/CXCL9 showed high bactericidal activity against. P. aeruginosa, including some strains from the airways of CF patients. Full-length MIG/CXCL9 was detected in sputum from healthy controls and CF patients colonized with P. aeruginosa. However, degraded MIG/CXCL9 was only found in CF sputum. In vitro, elastase of P. aeruginosa cleaved off a fragment of similar size and two additional fragments from MIG/CXCL9. The fragments showed less bactericidal activity against P. aeruginosa compared with the full-length protein. The fragments did not activate the MIG/CXCL9 receptor CXCR3 (expressed e.g. by NK cells, mast cells, and activated T cells) but instead displayed noncompetitive inhibition. In vitro, a decrease in CXCR3-bearing cells was found within and in the proximity of the bronchial epithelium of CF lung tissue compared with controls. Taken together, both bactericidal and cell-recruiting activities of MIG/CXCL9 are corrupted by P. aeruginosa through release of elastase, and this may contribute to impaired airway host defense in CF. © 2014 S. Karger AG, Basel.},
  author       = {Jovic, Sandra and Shikhagaie, Medya and Mörgelin, Matthias and Kjellström, Sven and Erjefält, Jonas and Olin, Anders and Frick, Inga-Maria and Egesten, Arne},
  issn         = {1662-811X},
  language     = {eng},
  number       = {6},
  pages        = {846--859},
  publisher    = {Karger},
  series       = {Journal of Innate Immunity},
  title        = {Expression of MIG/CXCL9 in Cystic Fibrosis and Modulation of Its Activities by Elastase of Pseudomonas aeruginosa.},
  url          = {http://dx.doi.org/10.1159/000365399},
  volume       = {6},
  year         = {2014},
}