Impairment of neutrophil reactivity to elastin peptides in COPD.

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.

• Authors: Aurélie Dupont, Sandra Dury, Valérie Gafa, François Lebargy, Gaëtan Deslée, Moncef Guenounou, Frank Antonicelli, Richard Le Naour
• Journal: Thorax (Thorax) Vol. 68 Issue 5 Pg. 421-8 (May 2013) ISSN: 1468-3296 [Electronic] England
• PMID: 23359459 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Cytokines
• Reactive Oxygen Species
• Receptors, Cell Surface
• elastin-binding proteins
• Elastin

Topics

• Aged
• Cells, Cultured
• Chemotaxis
• Cytokines (biosynthesis)
• Elastin
• Female
• Flow Cytometry
• Humans
• Leukocyte Count
• Male
• Middle Aged
• Neutrophil Activation
• Neutrophils (metabolism, pathology)
• Pulmonary Disease, Chronic Obstructive (metabolism, pathology)
• Reactive Oxygen Species (metabolism)
• Receptors, Cell Surface (biosynthesis)
• Smoking (adverse effects)
• Sputum (cytology, metabolism)