2002 Fiscal Year Final Research Report Summary
Smoking susceptibility and pathogenesis of pulmonary emphysema
| Project/Area Number |
13470125
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Respiratory organ internal medicine
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| Research Institution | HOKKAIDO UNIVERSITY |
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Principal Investigator |
NISHIMURA Masaharu Hokkaido Univ., Grad. School of Med., Prof., 大学院・医学研究科, 教授 (00208224)
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| Co-Investigator(Kenkyū-buntansha) |
BETSUYAKU Tomoko Hokkaido Univ., Medical Hospital, Instractor., 医学部付属病院, 助手 (60333605)
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| Project Period (FY) |
2001 – 2002
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| Keywords | smoking / epithelial cell / gene / genechip / adenovirus / pulmonary emphysema / neutrophil / macrophage |
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| Research Abstract |
Cigarette smoking is the major cause of chronic obstructive pulmonary disease (COPD) and it is generally accepted that proteinases released from neutrophils and/or macrophages are involved in the development of emphysema. It remained unknown why only a small portion of smokers develops clinically apparent emphysema and which cells and/or proteinases play a key role in the pathogenesis of COPD. Using bronchoalveolar lavage (BAL) to compare asymptomatic smokers having emphysema detected by CT scans with individuals who have a similar smoking history but do not have emphysema, we have demonstrated that (1) the concentration of neutrophil-derived granular proteins are significantly elevated in BAL fluid in the subjects with subclinical emphysema, and the level of NE-□1PI correlates with the level of neutrophil chemoattractant, interleukin-8 (IL-8) in BAL fluid. These data provide evidence for neutrophil involvement, in which IL-8 might play a key role, in the early stage of development of
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pulmonary emphysema. Bronchiolar epithelium is known to be a potential source of IL-8, and has a critical role in repair of epithelium and structural remodeling as studied in fibrosing lung injuries. Although smoking is known to affect lung structure and function in diverse ways, a comprehensive assessment of smoking's effects on pulmonary gene expression has not been done. Accordingly, we have subjected C57B6 mice to the smoke of cigarettes for up to 6 months and examined gene expression of terminal bronchiolar epithelium. As we first established, we used laser capture microdissection (LCM) to isolate terminal bronchiolar epithelial cells from frozen sections of lungs. The RNA isolated from LCM-obtained cells was subjected to two rounds of linear amplification to apply to high-density oligonucleotide arrays (GeneChips ; Affymetrix). These results show theat a variety of bronchiolar cell genes are affected quickly by smoking and that the gene profile is changed by chronic exposure, providing the molecular information of bronchiolar epithelium in the pathogenesis of COPD. Less
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