Impairment of neutrophil reactivity to elastin peptides in COPD.
BACKGROUND
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).


OBJECTIVE
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.
EA4683, SFR CAP-Santé, Université de Reims Champagne-Ardenne, Reims, France.
Aurélie
A
Dupont
Sandra
S
Dury
Valérie
V
Gafa
François
F
Lebargy
Gaëtan
G
Deslée
Moncef
M
Guenounou
Frank
F
Antonicelli
Richard
R
Le Naour
D000368:Aged; D002478:Cells, Cultured; D002633:Chemotaxis; D016207:Cytokines / Q000096:biosynthesis*; D004549:Elastin; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007958:Leukocyte Count; D008297:Male; D008875:Middle Aged; D018375:Neutrophil Activation; D009504:Neutrophils / Q000378:metabolism* / Q000473:pathology; D029424:Pulmonary Disease, Chronic Obstructive / Q000378:metabolism* / Q000473:pathology; D017382:Reactive Oxygen Species / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000096:biosynthesis*; D012907:Smoking / Q000009:adverse effects; D013183:Sputum / Q000166:cytology / Q000378:metabolism
D016207:Cytokines; D017382:Reactive Oxygen Species; D011956:Receptors, Cell Surface; C054901:elastin-binding proteins; D004549:Elastin