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The neutrophil-recruiting chemokine GCP-2/CXCL6 is expressed in cystic fibrosis airways and retains its functional properties after binding to extracellular DNA.

Jovic, Sandra LU ; Linge, Helena LU ; Shikhagaie, Medya LU ; Olin, Anders LU ; Lannefors, Louise LU ; Erjefält, Jonas LU ; Mörgelin, Matthias LU and Egesten, Arne LU (2016) In Mucosal Immunology 9(1). p.112-123
Abstract
Infections in cystic fibrosis (CF), often involving Pseudomonas aeruginosa, result from a dysregulated airway immunity where one hallmark is the accumulation of necrotic and apoptotic immune cells, in particular neutrophils. In addition, neutrophils actively release DNA, forming neutrophil extracellular traps (NETs) that contain antimicrobial proteins. Altogether, free DNA in complex with actin accumulates in the airway lumen, resulting in highly viscous sputum that provides an anionic matrix, binding cationic antimicrobial proteins. In this study, granulocyte chemotactic protein 2 (GCP-2)/CXCL6, a neutrophil-activating chemokine with bactericidal properties, was detected in the airway epithelium of CF patients and was also present in... (More)
Infections in cystic fibrosis (CF), often involving Pseudomonas aeruginosa, result from a dysregulated airway immunity where one hallmark is the accumulation of necrotic and apoptotic immune cells, in particular neutrophils. In addition, neutrophils actively release DNA, forming neutrophil extracellular traps (NETs) that contain antimicrobial proteins. Altogether, free DNA in complex with actin accumulates in the airway lumen, resulting in highly viscous sputum that provides an anionic matrix, binding cationic antimicrobial proteins. In this study, granulocyte chemotactic protein 2 (GCP-2)/CXCL6, a neutrophil-activating chemokine with bactericidal properties, was detected in the airway epithelium of CF patients and was also present in azurophilic and specific granules of neutrophils. Elastase of neutrophils, but not of P. aeruginosa, completely degraded CXCL6 (chemokine (C-X-C motif) ligand 6). In addition, CXCL6 colocalized with extracellular DNA in both CF sputa and in in vitro-formed NETs. In vitro, CXCL6 bound DNA with a KD of 2,500 nM. Interestingly, both the bactericidal and the receptor-activating properties of CXCL6 (against neutrophils) remained largely unaffected in the presence of DNA. However, the chemotactic properties of CXCL6 were reduced by the presence of DNA. Taken together, CXCL6 is expressed in CF, retaining its functional properties even after binding to the anionic scaffold that extracellular DNA provides in CF.Mucosal Immunology advance online publication, 20 May 2015; doi:10.1038/mi.2015.43. (Less)
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author
organization
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type
Contribution to journal
publication status
published
subject
in
Mucosal Immunology
volume
9
issue
1
pages
112 - 123
publisher
Nature Publishing Group
external identifiers
  • pmid:25993443
  • wos:000367653800009
  • scopus:84953249983
ISSN
1933-0219
DOI
10.1038/mi.2015.43
language
English
LU publication?
yes
id
7d66f83f-ba6e-4440-8e79-a43197c283e7 (old id 5448515)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/25993443?dopt=Abstract
date added to LUP
2015-06-05 11:12:58
date last changed
2017-05-28 03:05:34
@article{7d66f83f-ba6e-4440-8e79-a43197c283e7,
  abstract     = {Infections in cystic fibrosis (CF), often involving Pseudomonas aeruginosa, result from a dysregulated airway immunity where one hallmark is the accumulation of necrotic and apoptotic immune cells, in particular neutrophils. In addition, neutrophils actively release DNA, forming neutrophil extracellular traps (NETs) that contain antimicrobial proteins. Altogether, free DNA in complex with actin accumulates in the airway lumen, resulting in highly viscous sputum that provides an anionic matrix, binding cationic antimicrobial proteins. In this study, granulocyte chemotactic protein 2 (GCP-2)/CXCL6, a neutrophil-activating chemokine with bactericidal properties, was detected in the airway epithelium of CF patients and was also present in azurophilic and specific granules of neutrophils. Elastase of neutrophils, but not of P. aeruginosa, completely degraded CXCL6 (chemokine (C-X-C motif) ligand 6). In addition, CXCL6 colocalized with extracellular DNA in both CF sputa and in in vitro-formed NETs. In vitro, CXCL6 bound DNA with a KD of 2,500 nM. Interestingly, both the bactericidal and the receptor-activating properties of CXCL6 (against neutrophils) remained largely unaffected in the presence of DNA. However, the chemotactic properties of CXCL6 were reduced by the presence of DNA. Taken together, CXCL6 is expressed in CF, retaining its functional properties even after binding to the anionic scaffold that extracellular DNA provides in CF.Mucosal Immunology advance online publication, 20 May 2015; doi:10.1038/mi.2015.43.},
  author       = {Jovic, Sandra and Linge, Helena and Shikhagaie, Medya and Olin, Anders and Lannefors, Louise and Erjefält, Jonas and Mörgelin, Matthias and Egesten, Arne},
  issn         = {1933-0219},
  language     = {eng},
  number       = {1},
  pages        = {112--123},
  publisher    = {Nature Publishing Group},
  series       = {Mucosal Immunology},
  title        = {The neutrophil-recruiting chemokine GCP-2/CXCL6 is expressed in cystic fibrosis airways and retains its functional properties after binding to extracellular DNA.},
  url          = {http://dx.doi.org/10.1038/mi.2015.43},
  volume       = {9},
  year         = {2016},
}