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Chemokines in Bronchiolar Epithelium in the Development of Chronic Obstructive Pulmonary Disease

First Department of Medicine and Second Department of Surgery, Hokkaido University School of Medicine, Sapporo, Japan

Address correspondence to: Tomoko Betsuyaku, M.D., Ph.D., First Department of Medicine, Hokkaido University School of Medicine, N-15, W-7, Kita-ku, Sapporo, Japan, 060-8638. E-mail: bytomoko{at}med.hokudai.ac.jp

The inflammatory chemokines interleukin-8, macrophage inflammatory protein-1, and monocyte chemoattractant protein-1, are reportedly involved in the pathogenesis of chronic obstructive pulmonary disease (COPD). Although bronchiolar epithelial cells and macrophages are known to be the cellular sources, the relative contribution of each cell type remains to be elucidated. In the present study, we first quantified cytokine mRNA in human bronchiolar epithelial cells and macrophages obtained using laser-capture microdissection and explored the relationship with early-stage COPD. Only in bronchiolar epithelial cells were interleukin-8, macrophage inflammatory protein-1, and monocyte chemoattractant protein-1 mRNA levels higher in smokers with airflow limitation and/or emphysema than those in never-smokers or smokers without either airflow limitation or emphysema. No difference was observed in macrophages. Complementary DNA (cDNA) array further revealed the overexpression of CC chemokine receptor 2 in bronchiolar epithelial cells from smokers with airflow limitation and/or emphysema. This study supports the role of bronchiolar epithelium as the source of increased inflammatory chemokine levels in the early development of COPD and also demonstrates the potential use of laser-capture microdissection, combined with reverse transcriptase–polymerase chain reaction and cDNA microarrays, to investigate functional profiles of individual structural and inflammatory cells in human lungs.

Abbreviations: bronchoalveolar lavage, BAL • CC chemokine receptor 2, CCR2 • cluster of differentiation 68, CD68 • complementary DNA, cDNA • computed tomography, CT • chronic obstructive pulmonary disease, COPD • forced expiratory volume in one second, FEV₁ • forced vital capacity, FVC • glyceraldehyde-3-phosphatase-dehydrogenase, GAPDH • horseradish peroxidase, HRP • interleukin, IL • laser-capture microdissection, LCM • monocyte chemoattractant protein, MCP • macrophage inflammatory protein, MIP • phosphate-buffered saline, PBS • reverse transcriptase–polymerase chain reaction, RT-PCR

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