| Project/Area Number |
09670609
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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 | KYOTO UNIVERSITY |
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Principal Investigator |
AMITANI Ryouichi Guraduate School of Medicine, KYOTO UNIVERSITY Lecturer, 医学研究科, 講師 (70167964)
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| Co-Investigator(Kenkyū-buntansha) |
TANAKA Eisaku Graduate School of Medicine, KYOTO UNIVERSITY Lecturer, 医学研究科, 講師 (30183461)
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| Project Period (FY) |
1997 – 1998
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| Project Status |
Completed (Fiscal Year 1998)
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| Budget Amount *help |
¥2,800,000 (Direct Cost: ¥2,800,000)
Fiscal Year 1998: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 1997: ¥1,800,000 (Direct Cost: ¥1,800,000)
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| Keywords | Aspergillus species / Aspergillus fumigatus / bronchial mucosa / organ culture / epithelial damage / endocytosis / ultrastructure / Endocytosis / オーガン・カルチャー / 気道上皮傷害 / endocytosis / オ-ガン・カルチャー |
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| Research Abstract |
We have studied interactions of a clinical isolate of Aspergillus fumigatus with human bronchial mucosa in an organ culture model with an air-mucosal interface. A.fumigatus conidia were inoculated on the organ culture tissues, and incubated at 37ﾟC At each timepoint (1,6,12,18 and 24h), attachment and invasion of the bronchial mucosa by A.fumigatus conidia (and hyphae) as well as structural changes of the ciliated epithelium were investigated by scanning and transmission electron microscopy(SEM and TEM). EM demonstrated remarkable epithelial damage including separation of intercellular junction, extrusion and detachment of ciliated cells at 12 to 24h. SEM and TEM revealed attachment of conidia on the surface of the mucosa, some of which were associated with indentation on the epithelial surface at 1 to 6 h, internalization of conidia within the ciliated cells and intercellular conidia in the epithelium at 6 h, and hyphae directly penetrating epithelial cells as well as invading the intercellular space of the epithelium at 18 and 24 h. Pretreatment of the bronchial organ culture tissues with colchicine (microtubule inhibitor) or cytochalasin D (actin filament inhibitor) significantly suppressed the attachment and internalization of conidia in the respiratory epithelial cells.
It is suggested that A.fumigatus can invade the human bronchial ciliated epithelium by at least three different mechanisms internalization of conidia within epithelial cells which may be associated with cytoskeleton system of the epithelial cells, penetration of conidia (or hyphae) through the intercellular space of the epithelium, and direct penetration of hyphae through the intracellular space of ciliated epithelium associated with destruction of cytoplasmic membrane of the epithelial cells.
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