| Project/Area Number |
15590829
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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 | Tokyo Women's Medical University |
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Principal Investigator |
AOSHIBA Kazutetsu Tokyo Women's Medical University, School of Medicine, Assistant Professor, 医学部, 講師 (60231776)
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| Co-Investigator(Kenkyū-buntansha) |
KAMEYAMA Shinkichi Tokyo Women's Medical University, School of Medicine, Instructor, 医学部, 助手 (50214557)
角田 裕美 東京女子医科大学, 医学部, 助手 (30318109)
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| Project Period (FY) |
2003 – 2004
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| Project Status |
Completed (Fiscal Year 2004)
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| Budget Amount *help |
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2004: ¥1,700,000 (Direct Cost: ¥1,700,000)
Fiscal Year 2003: ¥1,800,000 (Direct Cost: ¥1,800,000)
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| Keywords | Chronic obstrulctive pulmonary disease / pulmonary emphysema / bone marrow stem cells / G-CSF / M-CSF / erythropoietin / G-CSF / 肺線維症 |
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| Research Abstract |
In this study, we examined whether bone marrow cells(BMCs) regenerate emphysematous lungs following elastase injury. Eight-week old female C57BL/6J mice were intratracheally administered porcine pancreatic elastase. One month later, they were intravenously administered either phosphate-buffered saline(PBS) or 5 x 10^6 BMCs harvested from 8-week-old male C57BL/6J mice. Three months later, the mice were sacrificed and lung histology was assessed. The number of alveoli in emphysematous lesions was significantly increased in the BMC treated mice as compared with the PBS-treated mice (51.8±18.8/mm^2 versus 23.3±6.7/mm^2,p=0.02). The mean alveolar cord length (a measure of alveolar size) tended to be decreased in the BMC-treated mice. Fluorescent in situ hybridization for the Y-chromosome revealed that donor BMCs had differentiated into alveolar epithelial cells in recipient mice. These results indicate that transplanted BMCs regenerate emphysematous lungs following elastase injury.
We also determined whether systemic administration of macrophage colony-stimulating factor(M-CSF) leads to regeneration of lungs in a murine model of elastase-induced emphysema. M-CSF administration without prior elastase did not affect mean linear intercept(Lm), surface area(Sa), or surface area/lung volume(Sa/LV). In contrast, M-CSF administration following elastase injury caused a greater increase in Lm and greater decreases in Sa and Sa/LV than saline administration following elastase, indicating that M-CSF aggravated emphysema. This aggravation of emphysema was accompanied by accumulation of pulmonary alveolar macrophages(AMs) expressing metalloproteinases(MMPs ) -9 and -12. M-CSF stimulated AMs to express MMPs in vitro. These results suggest that M-CSF administration does not support lung regeneration but rather aggravates the lung destruction associated with elastase injury.
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