| Project/Area Number |
16591724
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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 |
Otorhinolaryngology
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| Research Institution | JICHI MEDICAL SCHOOL |
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Principal Investigator |
ICHIMURA Keiichi JICHI MEDICAL SCHOOL, School of Medicine, Professor, 医学部, 教授 (00010471)
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| Co-Investigator(Kenkyū-buntansha) |
NISHINO Hiroshi JICHI MEDICAL SCHOOL, School of Medicine, Associate Professor, 医学部, 助教授 (50245057)
TANAKA Hidetaka JICHI MEDICAL SCHOOL, School of Medicine, Instructor, 医学部, 助手 (50296109)
SEJIMA Takayuki JICHI MEDICAL SCHOOL, School of Medicine, Fellow, 医学部, 研究員 (20326838)
石川 敏夫 自治医科大学, 医学部, 助手
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| Project Period (FY) |
2004 – 2005
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| Project Status |
Completed (Fiscal Year 2005)
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| Budget Amount *help |
¥3,400,000 (Direct Cost: ¥3,400,000)
Fiscal Year 2005: ¥1,700,000 (Direct Cost: ¥1,700,000)
Fiscal Year 2004: ¥1,700,000 (Direct Cost: ¥1,700,000)
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| Keywords | eosinophil / model animal / fibrinolytic system / remodeling / nasal polyps / fungus / アレルギー・喘息 / 微生物 / 動物モデル / 好酸球性炎症 / 鼻茸 / 副鼻腔炎 |
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| Research Abstract |
In response to increase in clinical interest in eosinophilic inflammation of the nose and sinuses and its concomitant polyp formation, we tried to create animal model of this condition for elucidating developing mechanism and clinical application. We transcutaneously opened rabbit maxillary sinuses and closed their ostia followed by instillation of inflammatory substances in order to create polyps. The world first formation of eosinophil dominant polyps was successfully performed by intradermal ovalbumin injection and intrasinus instillation of VGSG and MMP-2. Pretreatment of ovalbumin and instillation of VGSG may be inducing factors of eosinophilic inflammation by accelerating eosinophil infiltration and cause tissue change. MMP-2 might contribute to development of polyps by degrading type IV collagen and also be involved in remodeling by affecting extracellular matrix metabolism.
As fibrinolytic system is one of the major factors for controlling eosinophils and extracellular matrix, presence of fibrinolytic components in the nasal mucosa was verified. All components of fibrinolytic system including t-PA, u-PA, PAI-1 and PAI-2 were identified by RT-PCR. They were recognized in the epithelium and infiltrating cells by both in situ hybridization and immunohistochemical stains. The results indicated that fibrinolytic factors were intimately involved in developing polyps as they regulated enzymatic activity in remodeling. In order to investigate fungal contribution to eosinophilic inflammation of the nose and sinuses intrasinus Aspergillus instillation was tried. We have observed inflammatory findings of the mucosa but have not created edematous polyps so far. Further studies other than that with Aspergillus are required.
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