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Increased Expression of the Chemokine Receptor CXCR3 and Its Ligand CXCL10 in Peripheral Airways of Smokers with Chronic Obstructive Pulmonary Disease

Department of Clinical and Experimental Medicine, Section of Respiratory Diseases, University of Padova, Padova; BioXell, Milan; Research Center on Asthma and COPD, University of Ferrara, Ferrara; and Department of Respiratory Diseases, University of Modena and Reggio Emilia, Modena, Italy

Correspondence and requests for reprints should be addressed to Marina Saetta, Divisione di Pneumologia, Dipartimento di Medicina Clinica e Sperimentale, Università degli Studi di Padova, via Giustiniani 3, 35128 Padova, Italy. E-mail: marina.saetta{at}unipd.it

CXCR3 is a chemokine receptor preferentially expressed on lymphocytes, particularly on type-1 T-lymphocytes. Smokers who develop chronic obstructive pulmonary disease (COPD) have a chronic bronchopulmonary inflammation that is characterized by an increased infiltration of T-lymphocytes, particularly CD8⁺, in the airways and lung parenchyma. To investigate the expression of CXCR3 and its ligand interferon-induced protein 10/CXCL10 in COPD, we counted the number of CXCR3⁺ cells and analyzed the expression of CXCL10 in the peripheral airways of 19 patients undergoing lung resection for localized pulmonary lesions. We examined lung specimens from seven smokers with fixed airflow limitation (COPD), five smokers with normal lung function, and seven nonsmoking subjects with normal lung function. The number of CXCR3⁺ cells was immunohistochemically quantified in the epithelium, in the submucosa, and in the adventitia of peripheral airways. The number of CXCR3⁺ cells in the epithelium and submucosa was increased in smokers with COPD as compared with nonsmoking subjects, but not as compared with smokers with normal lung function. Immunoreactivity for the CXCR3-ligand CXCL10 was present in the bronchiolar epithelium of smokers with COPD but not in the bronchiolar epithelium of smoking and nonsmoking control subjects. Most CXCR3⁺ cells coexpressed CD8 and produced interferon . These findings suggest that the CXCR3/CXCL10 axis may be involved in the T cell recruitment that occurs in peripheral airways of smokers with COPD and that these T cells may have a type-1 profile.

Key Words: inflammation • type-1 lymphocytes • airflow limitation • smoking

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