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CXCR3 and CCR5 chemokines in the induced sputum from patients with COPD

¹Airway Disease, National Heart and Lung Institute, Imperial College London, Dovehouse Street, London, SW3 6LY, UK ²Laboratorio Multidisciplinar de Pesquisa, Hospital Universitário Clementino Fraga Filho/Federal University of Rio de Janeiro, Rio de Janeiro, Brazil

l.donnelly{at}imperial.ac.uk

Abstract

BackgroundCOPD is associated with increased numbers of CD4⁺ and CD8⁺ lymphocytes and macrophages in the small airways and lung parenchyma. The chemokines regulating T-cell recruitment into the lung are unknown but may involve CXCR3 and CCR5 chemoattractants. The aim of this study was to determine the concentrations of CXCR3 chemokines, CXCL9, CXCL10, CXCL11 and the CCR5 chemokine CCL5 in induced sputum from patients with COPD, smokers and non-smokers and to examine the relationship between chemokine expression, inflammatory cells and airway obstruction.

MethodsDifferential cell counts were performed and concentrations of CXCL9, CXCL10, CXCL11 and CCL5 were measured in induced sputum from non-smokers (n=18), smokers (n=20) and COPD patients (n=35) using ELISA.

ResultsThe concentrations of CXCL9, CXCL10, CXCL11 and CCL5 were significantly increased in the sputum of patients with COPD when compared with non-smokers but not smokers without obstruction (CXCL9: 14.3 (6. 5-99.3) vs. 1.4 (0-10.4), p<0.001 vs. 8.5 (0-16.0) pg/mL; CXCL10: 16.9 (6.2-148.8) vs. 3.7 (0-18.8), p<0.05 vs. 11.3 (3.7-46.7) pg/mL; CXCL11: 58.1 (34.5-85.3) vs. 33.5 (23.2-49.7), p<0.05 vs 49.8 (32.6-105.6) pg/mL; CCL5: 59.9 (57.1-67.8) vs. 33.5 (31.6-36.9) pg/ml, p<0.001). CCL5 in sputum from smokers was also significantly increased compared with that from non-smokers (63.0 (60.8-70.2) pg/mL p<0.001). There was a negative correlation between FEV₁% predicted, FEV₁/FVC ratio and percentage of macrophages, and all the chemokines analysed. Neutrophil numbers correlated positively with the concentrations of chemokines.

ConclusionsCXCR3 chemokines and CCL5 are increased in sputum from COPD patients compared with non-smokers, and may be important in COPD pathogenesis.

Key-words: Sputum, COPD, CXCR3, CCR5, chemokines