Association of increased CCL5 and CXCL7 chemokine expression with neutrophil activation in severe stable COPD

A. Di Stefano, G. Caramori, I. Gnemmi, M. Contoli, L. Bristot, A. Capelli, F. L M Ricciardolo, F. Magno, S. Ennio D'Anna, A. Zanini, M. Carbone, F. Sabatini, C. Usai, P. Brun, K. F. Chung, P. J. Barnes, A. Papi, I. M. Adcock, B. Balbi

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Abstract

Background: Increased numbers of activated neutrophils have been reported in the bronchial mucosa of patients with stable chronic obstructive pulmonary disease (COPD), particularly in severe disease. Objectives: To investigate the expression of neutrophilic chemokines and adhesion molecules in bronchial biopsies from patients with stable COPD of different severity (GOLD stages I-IV) compared with age-matched control subjects, smokers with normal lung function and never smokers. Methods: The expression of CCL5, CXCL1, 5, 6, 7 and 8, CXCR1, CXCR2, CD11b and CD44 was measured in the bronchial mucosa using immunohistochemistry, confocal immunofluorescence, real-time quantitative polymerase chain reaction (RT-QPCR) and Western blotting (WB). Results: The numbers of CCL5+ epithelial cells and CCL5+ and CXCL7+ immunostained cells were increased in the bronchial submucosa of patients with stable severe COPD compared with control never smokers and smokers with normal lung function. This was also confirmed at the level of mRNA expression. The numbers of CCL5+ cells in the submucosa of patients with COPD were 2-15 times higher than any other chemokines. There was no correlation between the number of these cells and the number of neutrophils in the bronchial submucosa. Compared with control smokers, the percentage of neutrophils coexpressing CD11b and CD44 receptors was significantly increased in the submucosa of patients with COPD. Conclusion: The increased expression of CCL5 and CXCL7 in the bronchial mucosa of patients with stable COPD, together with an increased expression of extracellular matrix-binding receptors on neutrophils, may be involved in the pathogenesis of COPD.

Original languageEnglish
Pages (from-to)968-975
Number of pages8
JournalThorax
Volume64
Issue number11
DOIs
Publication statusPublished - Nov 2009

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Chemokine CCL5
Neutrophil Activation
Chronic Obstructive Pulmonary Disease
Neutrophils
Mucous Membrane
Chemokines
Cell Count
Lung
Fluorescent Antibody Technique
Real-Time Polymerase Chain Reaction
Western Blotting
Epithelial Cells
Immunohistochemistry
Biopsy
Messenger RNA

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine

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Association of increased CCL5 and CXCL7 chemokine expression with neutrophil activation in severe stable COPD. / Di Stefano, A.; Caramori, G.; Gnemmi, I.; Contoli, M.; Bristot, L.; Capelli, A.; Ricciardolo, F. L M; Magno, F.; Ennio D'Anna, S.; Zanini, A.; Carbone, M.; Sabatini, F.; Usai, C.; Brun, P.; Chung, K. F.; Barnes, P. J.; Papi, A.; Adcock, I. M.; Balbi, B.

In: Thorax, Vol. 64, No. 11, 11.2009, p. 968-975.

Research output: Contribution to journalArticle

Di Stefano, A, Caramori, G, Gnemmi, I, Contoli, M, Bristot, L, Capelli, A, Ricciardolo, FLM, Magno, F, Ennio D'Anna, S, Zanini, A, Carbone, M, Sabatini, F, Usai, C, Brun, P, Chung, KF, Barnes, PJ, Papi, A, Adcock, IM & Balbi, B 2009, 'Association of increased CCL5 and CXCL7 chemokine expression with neutrophil activation in severe stable COPD', Thorax, vol. 64, no. 11, pp. 968-975. https://doi.org/10.1136/thx.2009.113647
Di Stefano, A. ; Caramori, G. ; Gnemmi, I. ; Contoli, M. ; Bristot, L. ; Capelli, A. ; Ricciardolo, F. L M ; Magno, F. ; Ennio D'Anna, S. ; Zanini, A. ; Carbone, M. ; Sabatini, F. ; Usai, C. ; Brun, P. ; Chung, K. F. ; Barnes, P. J. ; Papi, A. ; Adcock, I. M. ; Balbi, B. / Association of increased CCL5 and CXCL7 chemokine expression with neutrophil activation in severe stable COPD. In: Thorax. 2009 ; Vol. 64, No. 11. pp. 968-975.
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title = "Association of increased CCL5 and CXCL7 chemokine expression with neutrophil activation in severe stable COPD",
abstract = "Background: Increased numbers of activated neutrophils have been reported in the bronchial mucosa of patients with stable chronic obstructive pulmonary disease (COPD), particularly in severe disease. Objectives: To investigate the expression of neutrophilic chemokines and adhesion molecules in bronchial biopsies from patients with stable COPD of different severity (GOLD stages I-IV) compared with age-matched control subjects, smokers with normal lung function and never smokers. Methods: The expression of CCL5, CXCL1, 5, 6, 7 and 8, CXCR1, CXCR2, CD11b and CD44 was measured in the bronchial mucosa using immunohistochemistry, confocal immunofluorescence, real-time quantitative polymerase chain reaction (RT-QPCR) and Western blotting (WB). Results: The numbers of CCL5+ epithelial cells and CCL5+ and CXCL7+ immunostained cells were increased in the bronchial submucosa of patients with stable severe COPD compared with control never smokers and smokers with normal lung function. This was also confirmed at the level of mRNA expression. The numbers of CCL5+ cells in the submucosa of patients with COPD were 2-15 times higher than any other chemokines. There was no correlation between the number of these cells and the number of neutrophils in the bronchial submucosa. Compared with control smokers, the percentage of neutrophils coexpressing CD11b and CD44 receptors was significantly increased in the submucosa of patients with COPD. Conclusion: The increased expression of CCL5 and CXCL7 in the bronchial mucosa of patients with stable COPD, together with an increased expression of extracellular matrix-binding receptors on neutrophils, may be involved in the pathogenesis of COPD.",
author = "{Di Stefano}, A. and G. Caramori and I. Gnemmi and M. Contoli and L. Bristot and A. Capelli and Ricciardolo, {F. L M} and F. Magno and {Ennio D'Anna}, S. and A. Zanini and M. Carbone and F. Sabatini and C. Usai and P. Brun and Chung, {K. F.} and Barnes, {P. J.} and A. Papi and Adcock, {I. M.} and B. Balbi",
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T1 - Association of increased CCL5 and CXCL7 chemokine expression with neutrophil activation in severe stable COPD

AU - Di Stefano, A.

AU - Caramori, G.

AU - Gnemmi, I.

AU - Contoli, M.

AU - Bristot, L.

AU - Capelli, A.

AU - Ricciardolo, F. L M

AU - Magno, F.

AU - Ennio D'Anna, S.

AU - Zanini, A.

AU - Carbone, M.

AU - Sabatini, F.

AU - Usai, C.

AU - Brun, P.

AU - Chung, K. F.

AU - Barnes, P. J.

AU - Papi, A.

AU - Adcock, I. M.

AU - Balbi, B.

PY - 2009/11

Y1 - 2009/11

N2 - Background: Increased numbers of activated neutrophils have been reported in the bronchial mucosa of patients with stable chronic obstructive pulmonary disease (COPD), particularly in severe disease. Objectives: To investigate the expression of neutrophilic chemokines and adhesion molecules in bronchial biopsies from patients with stable COPD of different severity (GOLD stages I-IV) compared with age-matched control subjects, smokers with normal lung function and never smokers. Methods: The expression of CCL5, CXCL1, 5, 6, 7 and 8, CXCR1, CXCR2, CD11b and CD44 was measured in the bronchial mucosa using immunohistochemistry, confocal immunofluorescence, real-time quantitative polymerase chain reaction (RT-QPCR) and Western blotting (WB). Results: The numbers of CCL5+ epithelial cells and CCL5+ and CXCL7+ immunostained cells were increased in the bronchial submucosa of patients with stable severe COPD compared with control never smokers and smokers with normal lung function. This was also confirmed at the level of mRNA expression. The numbers of CCL5+ cells in the submucosa of patients with COPD were 2-15 times higher than any other chemokines. There was no correlation between the number of these cells and the number of neutrophils in the bronchial submucosa. Compared with control smokers, the percentage of neutrophils coexpressing CD11b and CD44 receptors was significantly increased in the submucosa of patients with COPD. Conclusion: The increased expression of CCL5 and CXCL7 in the bronchial mucosa of patients with stable COPD, together with an increased expression of extracellular matrix-binding receptors on neutrophils, may be involved in the pathogenesis of COPD.

AB - Background: Increased numbers of activated neutrophils have been reported in the bronchial mucosa of patients with stable chronic obstructive pulmonary disease (COPD), particularly in severe disease. Objectives: To investigate the expression of neutrophilic chemokines and adhesion molecules in bronchial biopsies from patients with stable COPD of different severity (GOLD stages I-IV) compared with age-matched control subjects, smokers with normal lung function and never smokers. Methods: The expression of CCL5, CXCL1, 5, 6, 7 and 8, CXCR1, CXCR2, CD11b and CD44 was measured in the bronchial mucosa using immunohistochemistry, confocal immunofluorescence, real-time quantitative polymerase chain reaction (RT-QPCR) and Western blotting (WB). Results: The numbers of CCL5+ epithelial cells and CCL5+ and CXCL7+ immunostained cells were increased in the bronchial submucosa of patients with stable severe COPD compared with control never smokers and smokers with normal lung function. This was also confirmed at the level of mRNA expression. The numbers of CCL5+ cells in the submucosa of patients with COPD were 2-15 times higher than any other chemokines. There was no correlation between the number of these cells and the number of neutrophils in the bronchial submucosa. Compared with control smokers, the percentage of neutrophils coexpressing CD11b and CD44 receptors was significantly increased in the submucosa of patients with COPD. Conclusion: The increased expression of CCL5 and CXCL7 in the bronchial mucosa of patients with stable COPD, together with an increased expression of extracellular matrix-binding receptors on neutrophils, may be involved in the pathogenesis of COPD.

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