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Original article
Impairment of neutrophil reactivity to elastin peptides in COPD
  1. Aurélie Dupont1,
  2. Sandra Dury1,2,
  3. Valérie Gafa1,
  4. François Lebargy1,2,
  5. Gaëtan Deslée2,3,
  6. Moncef Guenounou1,
  7. Frank Antonicelli4,
  8. Richard Le Naour1
  1. 1EA4683, SFR CAP-Santé, Université de Reims Champagne-Ardenne, Reims, France
  2. 2Service des Maladies Respiratoires, Centre Hospitalier Universitaire, Reims, France
  3. 3INSERM U903, SFR CAP-Santé, Université de Reims Champagne-Ardenne, Reims, France
  4. 4FRE3481, SFR CAP-Santé, Université de Reims Champagne-Ardenne, Reims, France
  1. Correspondence to Dr Richard Le Naour, EA4683, SFR CAP-Santé, ‘Immunité Adaptative et Fonctionnalité des Barrières Biologiques’, UFR de Pharmacie, Université de Reims Champagne-Ardenne, 1 rue du Marechal Juin, Reims cedex 51096, France; richard.lenaour{at}univ-reims.fr

Abstract

Rationale Neutrophils play an important role in the inflammatory process associated with chronic obstructive pulmonary disease (COPD). Lung-infiltrating neutrophils secrete elastinolytic proteases that participate in elastin breakdown and the formation of elastin peptides (EPs).

Objectives We hypothesized that circulating neutrophil-associated immune response may be modulated by EPs during COPD.

Methods Neutrophils obtained from patients with either stable or exacerbated COPD and controls were cultured with or without EPs. Cell chemotaxis was analysed by the Boyden method and cytokine expression was analysed by ELISA and real-time reverse transcriptase PCR. Bacterial phagocytosis and killing of ingested bacteria were evaluated after incubation with Pseudomonas aeruginosa. Reactive oxygen species (ROS) measurement and elastin receptor expression were determined by flow cytometry.

Results Chemotactic activity of neutrophils from patients with COPD towards the VGVAPG EP was reduced compared with controls. VGVAPG increased proinflammatory cytokine synthesis and bacterial load, but reduced ROS production in neutrophils from controls and from patients with stable COPD. Patients with exacerbated COPD were unresponsive to VGVAPG treatment. These findings were associated with a decreased or almost complete loss of S-Gal elastin receptor expression in neutrophils from patients with stable or exacerbated COPD, respectively.

Conclusions The study demonstrates that the response of neutrophils from patients with COPD to VGVAPG varied according to COPD phase and critical level of S-Gal expression. S-Gal downregulation could result from a feedback mechanism induced by high levels of EPs.

  • COPD Pathology
  • Innate Immunity
  • Neutrophil Biology

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