CXCR3 and CCR5 Chemokines in Induced Sputum From Patients With COPD

doi:10.1378/chest.07-0393

Chest

Volume 133, Issue 1, January 2008, Pages 26-33

https://doi.org/10.1378/chest.07-0393 Get rights and content

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.

Section snippets

Subjects

The study was approved by the Clementino Fraga Filho University Hospital–Federal University of Rio de Janeiro Ethics Committee, Brazil, and informed, written consent was obtained from each subject. Patients were recruited from the outpatient department of Pedro Ernesto University Hospital–Rio de Janeiro State University. Nonsmokers were recruited from the Thoracic Department of Federal University of Rio de Janeiro. Induced sputum supernatants were analyzed at the National Heart and Lung

Patient Characteristics

The patients with COPD who underwent induced sputum were significantly older than smokers and nonsmokers and had significantly lower FEV₁ percentage of predicted and FEV₁/FVC ratios (Table 1). There was no significant difference in the smoking history of COPD patients and smokers. Of the COPD patients, 6 subjects fulfilled the criteria for GOLD stage I, 13 subjects were GOLD stage II, 12 subjects were GOLD stage III, and 4 subjects were GOLD stage IV.

Induced-Sputum Cell Counts

The numbers of eosinophils and CD8⁺

Discussion

Induced sputum is safe and reliable, and is used increasingly to assess airway inflammation in several diseases, including COPD.²¹²²²³ Neutrophil counts are highly reproducible, but the repeatability of lymphocyte counts and measurements of inflammatory mediators in sputum are less reliable.²⁴ Use of DTT in sputum processing has been discussed by several authors²⁵²⁶ and is required for solubilization; however, it may interfere with disulphide bonds present in several chemokines and in

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This study was supported by the National Heart and Lung Institute, London, UK; Committee for Postgraduate Courses in Higher Education, Brazil; and National Council for Scientific and Technological Development, Brazil.

The authors have no conflicts of interest to disclose.

^†: Presently at the Division of Pulmonary Medicine, Pedro Ernesto University Hospital, State University of Rio de Janeiro School of Medicine, Rio de Janeiro, Brazil.

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Chest

Original ResearchCOPDCXCR3 and CCR5 Chemokines in Induced Sputum From Patients With COPD

Background

Methods

Results

Conclusions

Section snippets

Subjects

Patient Characteristics

Induced-Sputum Cell Counts

Discussion

Lancet

Chest

Trends Pharmacol Sci

Respir Med

J Lab Clin Med

Chest

The nature of small-airway obstruction in chronic obstructive pulmonary disease

N Engl J Med

CD8+ve cells in the lungs of smokers with chronic obstructive pulmonary disease

Am J Respir Crit Care Med

Lymphocytes, chronic bronchitis and chronic obstructive pulmonary disease

Novartis Found Symp

An immune basis for lung parenchymal destruction in chronic obstructive pulmonary disease and emphysema

PLoS Med

Increased expression of the chemokine receptor CXCR3 and its ligand CXCL10 in peripheral airways of smokers with chronic obstructive pulmonary disease

Am J Respir Crit Care Med

Regulation of TNF-α- and IFN-γ-induced CXCL10 expression: participation of the airway smooth muscle in the pulmonary inflammatory response in chronic obstructive pulmonary disease

FASEB J

The relative activity of CXCR3 and CCR5 ligands in T lymphocyte migration: concordant and disparate activitiesin vitroandin vivo

J Leukoc Biol

Interferon-inducible T cell α chemoattractant (I-TAC): a novel non-ELR CXC chemokine with potent activity on activated T cells through selective high affinity binding to CXCR3

J Exp Med

CCR3 functional responses are regulated by both CXCR3 and its ligands CXCL9, CXCL10 and CXCL11

Eur J Immunol

Original Research
COPD
CXCR3 and CCR5 Chemokines in Induced Sputum From Patients With COPD