Abstract
D6 is a “silent” chemokine-scavenging receptor involved in the intracellular degradation of pro-inflammatory chemokines and resolution of acute inflammatory responses in mice. Recently it has been found that D6 is increased in autoimmune diseases and in organ rejection conditions in humans. To investigate whether D6 is involved in the immune response in patients with COPD, we examined its expression by immunohistochemistry in surgically resected lung specimens from 3 groups of subjects: 16 smokers with COPD (FEV1=57±6%pred), 9 smokers with normal lung function (FEV1=102±3%) and 9 non-smoking controls (FEV1=106±6%). D6 was mainly detected in alveolar macrophages, where it was markedly up-regulated in smokers with COPD compared to control smokers and non-smokers [median (range): 78 (11-100%) vs 5 (0-61%) vs 0 (0-10%,) p<0.0005 for both]. D6 expression was confirmed at mRNA and protein levels by RT-PCR and FACS in alveolar macrophages, isolated from BAL. By immunofluorescence we observed that D6 co-localised mainly within the lysosome-associated macrophagic marker CD68. D6 expression in all patients was related to CD8 T-lymphocytes in alveolar walls (p=0.007,r=0.65) and to the degree of airway obstruction (p=0.0008,r= 0.57). In conclusion, this study shows for the first time that D6 is expressed in alveolar macrophages, is up-regulated in COPD patients and correlates with disease severity and number of CD8 T-lymphocytes. Although up-regulation of D6 may occur as an attempt to tune down inflammation, our results suggest that D6 may be playing an important role in the inflammatory, possibly autoimmune, mechanisms of COPD.
- © 2011 ERS