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CXCR3 and CCR5 Chemokines in Induced Sputum From Patients With COPD^*

Claudia Costa, MD; Rogerio Rufino, MD; Suzanne L. Traves, PhD; Jose Roberto Lapa e Silva, MD; Peter J. Barnes, DSc, FCCP and Louise E. Donnelly, PhD

^* From Airway Disease (Drs. Costa, Rufino, Traves, Barnes, and Donnelly), National Heart and Lung Institute, Imperial College London, London, UK; and Laboratorio Multidisciplinar de Pesquisa (Dr. Lapa e Silva), Hospital Universitário Clementino Fraga Filho/Federal University of Rio de Janeiro, Rio de Janeiro, Brazil. Presently at the Division of Pulmonary Medicine, Pedro Ernesto University Hospital, State University of Rio de Janeiro School of Medicine, Rio de Janeiro, Brazil.

Correspondence to: Louise E. Donnelly, PhD, Airway Disease, National Heart and Lung Institute, Dovehouse St, London, SW3 6LY, UK; e-mail: l.donnelly{at}imperial.ac.uk

Abstract

Background: COPD 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 aims of this study were to determine the concentrations of CXCR3 chemokines CXCL9, CXCL10, CXCL11, and the CCR5 chemokine CCL5 in induced sputum from patients with COPD, smokers, and nonsmokers, and to examine the relationship between chemokine expression, inflammatory cells, and airway obstruction.

Methods: Differential cell counts were performed and concentrations of CXCL9, CXCL10, CXCL11, and CCL5 were measured in induced sputum from nonsmokers (n = 18), smokers (n = 20), and COPD patients (n = 35) using an enzyme-linked immunosorbent assay.

Results: Concentrations of CXCL9, CXCL10, CXCL11, and CCL5 were significantly increased in the sputum of patients with COPD when compared with nonsmokers but not smokers without obstruction: CXCL9 (median, 14.3 pg/mL; interquartile range [IQR], 6.5 to 99.3; vs median, 1.4 pg/mL; IQR, 0 to 10.4 [p < 0.001]; vs 8.5 pg/mL; IQR, 0 to 16.0, respectively); CXCL10 (16.9 pg/mL; IQR, 6.2 to 148.8; vs 3.7 pg/mL; IQR, 0 to 18.8 [p < 0.05]; vs 11.3 pg/mL; IQR, 3.7 to 46.7); CXCL11 (58.1 pg/mL; IQR, 34.5 to 85.3; vs 33.5 pg/mL; IQR, 23.2 to 49.7 [p < 0.05]; vs 49.8 pg/mL; IQR, 32.6 to 105.6); and CCL5 (59.9 pg/mL; IQR, 57.1 to 67.8; vs 33.5 pg/mL; IQR, 31.6 to 36.9 [p < 0.001]). CCL5 in sputum from smokers was also significantly increased compared with that from nonsmokers (median, 63.0 pg/mL; IQR, 60.8 to70.2; p < 0.001). There was a negative correlation between FEV₁ percentage of predicted, FEV₁/FVC ratio, and percentage of macrophages, and all the chemokines analyzed. Neutrophil numbers correlated positively with the concentrations of chemokines.

Conclusions: CXCR3 chemokines and CCL5 are increased in sputum from COPD patients compared with nonsmokers, and may be important in COPD pathogenesis.

Key Words: CCR5 • chemokines • COPD • CXCR3 • sputum