Type

Journal Article

Authors

Noel G McElvaney
Emer P Reeves
Andreas J Kungl
Tiziana Adage
M Emmet O'Brien
Cormac McCarthy
Hilary Kerr
David A Bergin
Tanja Gerlza
Kerstin Pohl
and 4 others

Subjects

Biochemistry

Topics
cystic fibrosis recombinant proteins neutrophils enzyme linked immunosorbent assay metabolism bronchoalveolar lavage fluid proteolysis glycosaminoglycans young adult pathology interleukin 8 drug effects chemotaxis humans pharmacology

The effect of the decoy molecule PA401 on CXCL8 levels in bronchoalveolar lavage fluid of patients with cystic fibrosis. (2014)

Abstract The chemokine interleukin-8 (CXCL8) is a key mediator of inflammation in airways of patients with cystic fibrosis (CF). Glycosaminoglycans (GAGs) possess the ability to influence the chemokine profile of the CF lung by binding CXCL8 and protecting it from proteolytic degradation. CXCL8 is maintained in an active state by this glycan interaction thus increasing infiltration of immune cells such as neutrophils into the lungs. As the CXCL8-based decoy PA401 displays no chemotactic activity, yet demonstrates glycan binding affinity, the aim of this study was to investigate the anti-inflammatory effect of PA401 on CXCL8 levels, and activity, in CF airway samples in vitro. Bronchoalveolar lavage fluid (BALF) was collected from patients with CF homozygous for the ΔF508 mutation (n=13). CXCL8 in CF BALF pre and post exposure to PA401 was quantified by ELISA. Western blot analysis was used to determine PA401 degradation in CF BALF. The ex vivo chemotactic activity of purified neutrophils in response to CF airway secretions was evaluated post exposure to PA401 by use of a Boyden chamber-based motility assay. Exposure of CF BALF to increasing concentrations of PA401 (50-1000pg/ml) over a time course of 2-12h in vitro, significantly reduced the level of detectable CXCL8 (P<0.05). Interestingly, PA401 engendered release of CXCL8 from GAGs exposing the chemokine susceptible to proteolysis. Subsequently, a loss of PA401 was observed (P<0.05) due to proteolytic degradation by elastase like proteases. A 25% decrease in neutrophil chemotactic efficiency towards CF BALF samples incubated with PA401 was also observed (P<0.05). PA401 can disrupt CXCL8:GAG complexes, rendering the chemokine susceptible to proteolytic degradation. Clinical application of a CXCL8 decoy, such as PA401, may serve to decrease the inflammatory burden in the CF lung in vivo.
Collections Ireland -> Royal College of Surgeons in Ireland -> PubMed

Full list of authors on original publication

Noel G McElvaney, Emer P Reeves, Andreas J Kungl, Tiziana Adage, M Emmet O'Brien, Cormac McCarthy, Hilary Kerr, David A Bergin, Tanja Gerlza, Kerstin Pohl and 4 others

Experts in our system

1
Noel G McElvaney
Royal College of Surgeons in Ireland
Total Publications: 194
 
2
Emer P Reeves
Royal College of Surgeons in Ireland
Total Publications: 63
 
3
M Emmet O'Brien
Royal College of Surgeons in Ireland
Total Publications: 9
 
4
Cormac McCarthy
Royal College of Surgeons in Ireland
Total Publications: 19
 
5
David A Bergin
Royal College of Surgeons in Ireland
Total Publications: 28
 
6
Kerstin Pohl
Royal College of Surgeons in Ireland