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 infl ammatory responses in mice. Emerging evidence suggests that D6 might behave differently in human chronic infl ammatory conditions. We, therefore, investigated the involvement of D6 in the immune responses in COPD, a chronic infl ammatory condition of the lung. Methods: D6 expression was quantifi ed 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 fl cytometry, immunofl uorescence, 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 1 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 1 T lymphocytes, IL-32, tumor necrosis factor- a , B-cell activating factor of the tumor necrosis factor family, phospho-p38