Expression of the atypical chemokine receptor D6 in human alveolar macrophages in COPD

ABSTRACT BACKGROUND. D6 is an atypical chemokine receptor involved in chemokines 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 controls with normal lung function (9 smoking and 9 non-smoking). Bronchoalveolar lavage (BAL) was also obtained and analysed 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 (AM). The percentage of D6+ AM was markedly increased in COPD patients as compared to both smoking and non-smoking controls (p<0.0005 for both). D6 expression was detected at both transcript and protein level in AM but not in monocyte-derived macrophages. Finally, D6 expression was positively correlated with markers of immune activation (CD8+ T lymphocytes, IL-32, TNFα, BAFF, phospho-p38 MAPK) and negatively with lung function (FEV1, FEV1/FVC). CONCLUSIONS. D6 is expressed in alveolar macrophages from COPD patients and its expression correlates with the degree of functional impairment and markers of immune activation. Up-regulation of D6 in alveolar macrophages could indicate that, besides its known scavenger activity in acute inflammation, D6 may have additional roles in chronic inflammatory conditions possibly promoting immune activation.