CD8 chemokine receptors in chronic obstructive pulmonary disease.
Increased lung CD8 cells and their expression of chemokine receptors CXCR3 and CCR5 have been previously reported in chronic obstructive pulmonary disease (COPD). Alterations of CD8-CCR3 and -CCR4 expression and their ligands in COPD patients have not been fully investigated. The objective of this study was to assess in COPD patients: (i) broncho-alveolar lavage (BAL) CD8 CCR3 and CCR4 expression in COPD patients; and (ii) airway levels of the CCR3 ligands, CCL11 and CCL5. Multi-parameter flow cytometric analysis was used to assess BAL CD3 and CD8-chemokine receptor expression in COPD patients, smokers and healthy non-smokers (HNS). CCL5 and CCL11 levels were measured in BAL, and from the supernatants of lung resection explant cultures. CD8-CCR3 and -CCR5 expression (means) were increased in COPD patients (22% and 46% respectively) and smokers (20% and 45%) compared with HNS (3% and 22%); P < 0.05 for all comparisons. CD3CXCR3 expression was raised in smokers and COPD while CD8CXCR3 and CD3 and CD8 CCR4 expression was similar between groups. CD8CCR5 expression correlated to smoking pack years (r = 0.42, P = 0.01). COPD explants released more CCL5 compared with smokers (P = 0.02), while there was low level CCL11 production. CD8CCR3 and CCR5 expression appear to be regulated by cigarette smoke exposure. We show that COPD lung tissue released more CCL5, suggesting a role for CCL5-CCR3 signalling in pulmonary CD8 recruitment in COPD.
Smyth
L J C
LJ
North West Lung Centre, School of Translational Medicine, University of Manchester, Southmoor Road, Manchester, UK. ljcsmyth@yahoo.co.uk
Starkey
C
C
Gordon
F S
FS
Vestbo
J
J
Singh
D
D
D000368:Aged; D001992:Bronchoalveolar Lavage Fluid / Q000276:immunology*; D017252:CD3 Complex / Q000032:analysis; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D016022:Case-Control Studies; D054413:Chemokine CCL11 / Q000032:analysis; D018946:Chemokine CCL5 / Q000032:analysis; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D008297:Male; D008875:Middle Aged; D029424:Pulmonary Disease, Chronic Obstructive / Q000276:immunology*; D054397:Receptors, CCR3 / Q000032:analysis*; D054398:Receptors, CCR4 / Q000032:analysis*; D012907:Smoking / Q000276:immunology
C515354:CCR4 protein, human; D017252:CD3 Complex; D054413:Chemokine CCL11; D018946:Chemokine CCL5; D054397:Receptors, CCR3; D054398:Receptors, CCR4