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CXCL-8-dependent and -independent neutrophil activation in COPD: experiences from a pilot study of the CXCR2 antagonist danirixin

Holly R. Keir, Hollian Richardson, Christina Fillmore, Amelia Shoemark, Aili L. Lazaar, Bruce E. Miller, Ruth Tal-Singer, James D. Chalmers, Divya Mohan
ERJ Open Research 2020 6: 00583-2020; DOI: 10.1183/23120541.00583-2020
Holly R. Keir
1Ninewells Clinical Research Centre, University of Dundee, Dundee, UK
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Hollian Richardson
1Ninewells Clinical Research Centre, University of Dundee, Dundee, UK
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Christina Fillmore
2GSK R&D, Stevenage, UK
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Amelia Shoemark
1Ninewells Clinical Research Centre, University of Dundee, Dundee, UK
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  • ORCID record for Amelia Shoemark
Aili L. Lazaar
3GSK R&D, Collegeville, PA, USA
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Bruce E. Miller
3GSK R&D, Collegeville, PA, USA
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Ruth Tal-Singer
3GSK R&D, Collegeville, PA, USA
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  • ORCID record for Ruth Tal-Singer
James D. Chalmers
1Ninewells Clinical Research Centre, University of Dundee, Dundee, UK
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  • For correspondence: jchalmers@dundee.ac.uk
Divya Mohan
3GSK R&D, Collegeville, PA, USA
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    FIGURE 1

    a) Randomised controlled trial of danirixin (DNX) (n=14) versus placebo (n=5). Data are presented as median histone (H1)–elastase complexes (primary outcome) across the four trial visits. Note that this figure is generated from a post hoc analysis; the primary analysis was from the mixed model. b) Purified neutrophils from healthy donors (n=3) were stimulated with interleukin (IL)-8 (10 ng·mL−1) or Gro-α (1000 nM) in the presence or absence of DNX (10 μM). % change in CD11b expression was determined by fluorescence-activated cell sorting analysis of mean fluorescent intensity (IL-8 paired t-test, p=0.0165; Gro-α paired t-test, p=0.0187). c) Neutrophil activation is blocked in response to DNX in some, but not all, COPD samples, independent of IL-8 sputum concentration; % reduction in CD11b expression after exposure of healthy volunteer neutrophils to 10% soluble sputum from patients with COPD in the presence of DNX (10 μM) against sputum IL-8 concentration (correlation, r=0.26, p=0.35). S: start of study; D1: day 1; D7: day 7; D14: day 14. *: p<0.05.

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ERJ Open Research: 6 (4)
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CXCL-8-dependent and -independent neutrophil activation in COPD: experiences from a pilot study of the CXCR2 antagonist danirixin
Holly R. Keir, Hollian Richardson, Christina Fillmore, Amelia Shoemark, Aili L. Lazaar, Bruce E. Miller, Ruth Tal-Singer, James D. Chalmers, Divya Mohan
ERJ Open Research Oct 2020, 6 (4) 00583-2020; DOI: 10.1183/23120541.00583-2020

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CXCL-8-dependent and -independent neutrophil activation in COPD: experiences from a pilot study of the CXCR2 antagonist danirixin
Holly R. Keir, Hollian Richardson, Christina Fillmore, Amelia Shoemark, Aili L. Lazaar, Bruce E. Miller, Ruth Tal-Singer, James D. Chalmers, Divya Mohan
ERJ Open Research Oct 2020, 6 (4) 00583-2020; DOI: 10.1183/23120541.00583-2020
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