Pregnancy Zone Protein is Associated with Airway Infection, Neutrophil Extracellular Trap Formation and Disease Severity in Bronchiectasis

Simon Finch, Amelia Shoemark, Alison J. Dicker, Holly R. Keir, Alexandria Smith, Samantha Ong, Brandon Tan, Jean-yu Choi, Thomas C. Fardon, Diane Cassidy, Jeffrey T. J. Huang, James D. Chalmers (Lead / Corresponding author)

Research output: Contribution to journalArticle

1 Citation (Scopus)
135 Downloads (Pure)

Abstract

Rationale: PZP (pregnancy zone protein) is a broad-spectrum immunosuppressive protein believed to suppress T-cell function during pregnancy to prevent fetal rejection. It has not previously been reported in the airway.Objectives: To characterize PZP in the bronchiectasis airway, including its relationship with disease severity.Methods: Label-free liquid chromatography/mass spectrometry was performed for sputum protein profiling of patients with bronchiectasis confirmed by high-resolution computed tomography. Results for patients with and without Pseudomonas aeruginosa infection were compared. Sputum and serum PZP was measured by validated ELISA. Airway infection status was established by culture and 16S ribosomal RNA sequencing. Immunofluorescence, ELISA, and electron microscopy were used to identify the cellular source of PZP in neutrophils treated with multiple stimuli.Measurements and Main Results: Elevated PZP was identified by label-free liquid chromatography/mass spectrometry as being associated with P. aeruginosa infection. In a validation study of 124 patients, sputum but not serum concentrations of PZP were significantly associated with the Bronchiectasis Severity Index, the frequency of exacerbations, and symptoms. Airway infection with Proteobacteria such as P. aeruginosa was associated with higher concentrations of PZP. PZP in sputum was directly related to airway bacterial load. Neutrophils induced to form neutrophil extracellular traps (NETs) with phorbol myristate acetate released high concentrations of PZP in vitro, and fluorescence microscopy confirmed the presence of PZP in NETs, whereas fluorescence and electron microscopy localized PZP to the cytoplasm and nuclei of neutrophils. Effective antibiotic therapy reduced sputum PZP.Conclusions: PZP is released into NETs. We report a novel link between airway infection, NET formation, and disease severity in bronchiectasis during chronic airway inflammation.

Original languageEnglish
Pages (from-to)992-1001
Number of pages10
JournalAmerican Journal of Respiratory and Critical Care Medicine
Volume200
Issue number8
Early online date2 Jul 2019
DOIs
Publication statusPublished - 15 Oct 2019

Keywords

  • bronchiectasis
  • exacerbations
  • microbiome
  • neutrophils

Fingerprint Dive into the research topics of 'Pregnancy Zone Protein is Associated with Airway Infection, Neutrophil Extracellular Trap Formation and Disease Severity in Bronchiectasis'. Together they form a unique fingerprint.

  • Profiles

    No photo of James Chalmers

    Chalmers, James

    Person: Academic

    No photo of Jeffrey Huang

    Huang, Jeffrey

    Person: Academic Related, Research

    Cite this