| Project/Area Number |
17590801
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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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 | Wakayama Medical University |
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Principal Investigator |
YAMAGATA Toshiyuki Wakayama Medical University, School of Medicine, Assistant Professor (80285410)
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| Co-Investigator(Kenkyū-buntansha) |
ICHINOSE Masakazu Wakayama Medical University, School of Medicine, Professor (80223105)
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| Project Period (FY) |
2005 – 2007
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| Project Status |
Completed (Fiscal Year 2007)
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| Budget Amount *help |
¥3,600,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥300,000)
Fiscal Year 2007: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2006: ¥1,200,000 (Direct Cost: ¥1,200,000)
Fiscal Year 2005: ¥1,100,000 (Direct Cost: ¥1,100,000)
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| Keywords | Chronic obstructive pulmonary disease / Airway inflammation / Neutrophils / Integrin / Chemokine receptor / Hck |
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| Research Abstract |
Neutrophils are thought to play an important role in the pathophysiology of chronic obstructive pulmonary disease (COPD). There are various molecules involved in migration and activation of neutrophils in airways. However, the intracellular signal transduction pathways, which cause infiltration and activation of neutrophils in airways, are still unclear. The aim of the present study was to investigate the various molecules expression including integrin, chemokine receptor (CXCR) and hematopoietic cell kinase (Hck) in peripheral blood neutrophils and to clarify their possible role in the pathophysiology of COPD.
The surface expression of integrin (CD-11b / CD-18), CXC receptor 1 and 2 (CXCR1, CXCR2) of circulating neutrophils from COPD patients and healthy subjects (HS) was measured by flow cytometry analysis. The protein level of Hck and phosphorylated-Hck (p-Hck) were measured by Western blotting.
Both CD-11b and CXCR1 expression were significantly higher in COPD patients than in HS. The expression of CD-11b and CXCR1 showed a significant negative correlation with the severity of airflow limitation. The Hck protein level was also significantly higher in COPD patients compared with HS. This increase in Hck protein also negatively correlated with the severity of airflow limitation. In addition, significant correlation was seen between the protein level of Hck and the surface expression of CD-11b or CXCR1. In contrast, the p-Hck protein levels showed no difference between COPD patients and HS.
The over expression of CD-11b and CXCR1 on circulating neutrophils may be associated with the development of airflow limitation in COPD. In addition, the expression of Hck protein in peripheral blood neutrophils might also play an important role in the development of COPD. These results suggest that integrin, CXCR or Hck might be novel biomarkers for COPD monitoring and the modulation of these molecules expression might be a promising therapeutic target in COPD.
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