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Original Research: COPD |

Expression of the Atypical Chemokine Receptor D6 in Human Alveolar Macrophages in COPDD6 Upregulation in COPD

Erica Bazzan, PhD; Marina Saetta, MD, FCCP; Graziella Turato, PhD; Elena M. Borroni, PhD; Cinzia Cancellieri, MSc; Simonetta Baraldo, PhD; Benedetta Savino, PhD; Fiorella Calabrese, MD; Andrea Ballarin, MD; Elisabetta Balestro, MD; Alberto Mantovani, MD; Manuel G. Cosio, MD; Raffaella Bonecchi, PhD; Massimo Locati, MD
Author and Funding Information

From the Department of Cardiac, Thoracic, and Vascular Sciences (Drs Bazzan, Saetta, Turato, Baraldo, Calabrese, Ballarin, Balestro, and Cosio), University of Padova and Padova City Hospital, Padova; the Humanitas Clinical and Research Center (Drs Borroni, Savino, Mantovani, Bonecchi, and Locati and Ms Cancellieri), I-20089 Rozzano (Milan); the Department of Medical Biotechnologies and Translational Medicine (Drs Borroni, Savino, Mantovani, Bonecchi, and Locati and Ms Cancellieri), University of Milan, I-20089 Rozzano (Milan), Italy; and the Respiratory Division at Royal Victoria Hospital and the Meakins-Christie Laboratories in the Department of Medicine (Dr Cosio), McGill University, Montreal, QB, Canada.

Correspondence to: Marina Saetta, MD, FCCP, Dipartimento di Scienze Cardiologiche Toraciche e Vascolari, Clinica Pneumologica, Via Giustiniani 3, 35128 Padova, Italy; e-mail: marina.saetta@unipd.it


Drs Bonecchi and Locati contributed equally to the study.

Funding/Support: This work was conducted in the context of High Specialty Center for Asthma and COPD (Padova) and with the support of the Fondazione Humanitas per la Ricerca (Rozzano, Milano). This study was supported by Ministero dell’Istruzione dell’Università e della Ricerca (MIUR) as PRIN and FIRB projects, the Italian Association for Cancer Research, Regione Lombardia (LIIN project), research grants of University of Padova, Fondazioni Cariparo and Cariplo, and The European Community’s Seventh Framework Programme [FP7-2007-2013] under grant agreement HEALTH-F4-2011-281608 (TIMER).

Reproduction of this article is prohibited without written permission from the American College of Chest Physicians. See online for more details.


Chest. 2013;143(1):98-106. doi:10.1378/chest.11-3220
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Background:  D6 is an atypical chemokine receptor involved in chemokine degradation and resolution of acute inflammatory responses in mice. Emerging evidence suggests that D6 might behave differently in human chronic inflammatory conditions. We, therefore, investigated the involvement of D6 in the immune responses in COPD, a chronic inflammatory condition of the lung.

Methods:  D6 expression was quantified by immunohistochemistry in surgical resected lung specimens from 16 patients with COPD (FEV1, 57% ± 6% predicted) and 18 control subjects with normal lung function (nine smokers and nine nonsmokers). BAL was also obtained and analyzed by flow cytometry, immunofluorescence, and molecular analysis for further assessment of D6 involvement.

Results:  D6 expression in the lung was mainly detected in alveolar macrophages (AMs). The percentage of D6+ AMs was markedly increased in patients with COPD as compared with both smoker and nonsmoker control subjects (P < .0005 for both). D6 expression was detected at both transcript and protein level in AMs but not in monocyte-derived macrophages. Finally, D6 expression was positively correlated with markers of immune activation (CD8+ T lymphocytes, IL-32, tumor necrosis factor-α, B-cell activating factor of the tumor necrosis factor family, phospho-p38 mitogen-activated protein kinase) and negatively with lung function (FEV1, FEV1/FVC).

Conclusions:  D6 is expressed in AMs from patients with COPD, and its expression correlates with the degree of functional impairment and markers of immune activation. Upregulation of D6 in AMs could indicate that, besides its known scavenger activity in acute inflammation, D6 may have additional roles in chronic inflammatory conditions possibly promoting immune activation.

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