Monocyte chemoattractant protein 1, interleukin 8, and chronic airways inflammation in COPD.
Chronic obstructive pulmonary disease (COPD) is one of the most common causes of death, with cigarette smoking among the main risk factors. Hallmarks of COPD include chronic airflow obstruction and chronic inflammation in the airway walls or alveolar septa. An earlier study reported elevated numbers of macrophages and mast cells within the bronchiolar epithelium in smokers with COPD, compared with smokers without. Since specific chemokines may be involved in this influx, the in situ protein and mRNA expression of monocyte chemoattractant protein 1 (MCP-1) and of interleukin 8 (IL-8) were studied in tumour-free peripheral lung tissue resected for lung cancer of current or ex-smokers with COPD (FEV(1)<75%; n=14) and without COPD (FEV(1)>84; n=14). MCP-1 was expressed by macrophages, T cells, and endothelial and epithelial cells. Its receptor, CCR2, is expressed by macrophages, mast cells, and epithelial cells. IL-8 was found in neutrophils, epithelial cells, and macrophages. In subjects with COPD, semi-quantitative analysis revealed 1.5-fold higher levels of MCP-1 mRNA and IL-8 mRNA and protein in bronchiolar epithelium (p<0.01) and 1.4-fold higher levels of CCR2 in macrophages (p=0.014) than in subjects without COPD. The bronchiolar epithelial MCP-1 mRNA expression correlated with both CCR2 expression on macrophages and mast cells (p<0.05) and the numbers of intra-epithelial macrophages and mast cells (p<0.04). The epithelial IL-8 expression did not correlate with the numbers of neutrophils, macrophages, CD45RO+, CD8+, or mast cells. These data suggest that MCP-1 and CCR2 are involved in the recruitment of macrophages and mast cells into the airway epithelium in COPD.
de Boer
W I
WI
Department of Pulmonology, Leiden University Medical Center, Leiden, The Netherlands. pdeboer@pulmonology.azl.nl
Sont
J K
JK
van Schadewijk
A
A
Stolk
J
J
van Krieken
J H
JH
Hiemstra
P S
PS
D000328:Adult; D000368:Aged; D001980:Bronchi / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000473:pathology; D018932:Chemokine CCL2 / Q000235:genetics / Q000378:metabolism*; D004848:Epithelium / Q000378:metabolism; D005260:Female; D006801:Humans; D007124:Immunoenzyme Techniques; D017403:In Situ Hybridization; D016209:Interleukin-8 / Q000235:genetics / Q000378:metabolism*; D008173:Lung Diseases, Obstructive / Q000378:metabolism*; D018655:Lymphocyte Count; D008297:Male; D008875:Middle Aged; D011650:Pulmonary Alveoli / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012189:Retrospective Studies
D018932:Chemokine CCL2; D016209:Interleukin-8; D012333:RNA, Messenger