Expression of the atypical chemokine receptor D6 in human alveolar macrophages in COPD.
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 (FEV(1), 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 (FEV(1), FEV(1)/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.
Department of Cardiac, Thoracic, and Vascular Sciences, University of Padova and Padova City Hospital, Padova.
Erica
E
Bazzan
Department of Cardiac, Thoracic, and Vascular Sciences, University of Padova and Padova City Hospital, Padova. Electronic address: marina.saetta@unipd.it.
Marina
M
Saetta
Department of Cardiac, Thoracic, and Vascular Sciences, University of Padova and Padova City Hospital, Padova.
Graziella
G
Turato
Humanitas Clinical and Research Center, I-20089 Rozzano (Milan), Italy; Department of Medical Biotechnologies and Translational Medicine, University of Milan, I-20089 Rozzano (Milan), Italy.
Elena M
EM
Borroni
Humanitas Clinical and Research Center, I-20089 Rozzano (Milan), Italy; Department of Medical Biotechnologies and Translational Medicine, University of Milan, I-20089 Rozzano (Milan), Italy.
Cinzia
C
Cancellieri
Department of Cardiac, Thoracic, and Vascular Sciences, University of Padova and Padova City Hospital, Padova.
Simonetta
S
Baraldo
Humanitas Clinical and Research Center, I-20089 Rozzano (Milan), Italy; Department of Medical Biotechnologies and Translational Medicine, University of Milan, I-20089 Rozzano (Milan), Italy.
Benedetta
B
Savino
Department of Cardiac, Thoracic, and Vascular Sciences, University of Padova and Padova City Hospital, Padova.
Fiorella
F
Calabrese
Department of Cardiac, Thoracic, and Vascular Sciences, University of Padova and Padova City Hospital, Padova.
Andrea
A
Ballarin
Department of Cardiac, Thoracic, and Vascular Sciences, University of Padova and Padova City Hospital, Padova.
Elisabetta
E
Balestro
Humanitas Clinical and Research Center, I-20089 Rozzano (Milan), Italy; Department of Medical Biotechnologies and Translational Medicine, University of Milan, I-20089 Rozzano (Milan), Italy.
Alberto
A
Mantovani
Department of Cardiac, Thoracic, and Vascular Sciences, University of Padova and Padova City Hospital, Padova; Respiratory Division at Royal Victoria Hospital and the Meakins-Christie Laboratories in the Department of Medicine, McGill University, Montreal, QB, Canada.
Manuel G
MG
Cosio
Humanitas Clinical and Research Center, I-20089 Rozzano (Milan), Italy; Department of Medical Biotechnologies and Translational Medicine, University of Milan, I-20089 Rozzano (Milan), Italy.
Raffaella
R
Bonecchi
Humanitas Clinical and Research Center, I-20089 Rozzano (Milan), Italy; Department of Medical Biotechnologies and Translational Medicine, University of Milan, I-20089 Rozzano (Milan), Italy.
Massimo
M
Locati
D000368:Aged; D016022:Case-Control Studies; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D007249:Inflammation / Q000378:metabolism; D008168:Lung / Q000378:metabolism*; D016676:Macrophages, Alveolar / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D029424:Pulmonary Disease, Chronic Obstructive / Q000378:metabolism*; D054447:Receptors, CCR10 / Q000378:metabolism*; D012129:Respiratory Function Tests; D012907:Smoking / Q000378:metabolism; D015854:Up-Regulation; D000097628:Chemokine Receptor D6
D054447:Receptors, CCR10; D000097628:Chemokine Receptor D6