1998 Fiscal Year Final Research Report Summary
In vivo培養法を用いた気道粘液過分泌機構の解明
| Project/Area Number |
08670673
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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 | Yokohama City University |
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Principal Investigator |
INAYAMA Yoshiaki Yokohama City University, School of Medicine, Assistant Professor, 医学部・附属病院, 講師 (10184730)
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| Co-Investigator(Kenkyū-buntansha) |
ASANO Satoshi Teijin Limited
MITSUHASHI Hiroaki Teijin Limited
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| Project Period (FY) |
1996 – 1998
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| Keywords | Airway epithelial cells / Mucus cell hyperplasia / Mucus hypersecretion / SLPI / elastase / culture model / MUC |
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| Research Abstract |
This research project primarily has been conducted, 1) to establish an in vivo culture model using denuded rat tracheal grafts repopulated with human airway epithelial cells, and 2) to clarify role of secretory leukoprotease inhibitor (SLPI) in various nonneoplastic conditions of human lungs.
Human airway bronchial cells were purchased from Clonetics Corp. and cultured several weeks in vitro in order to obtain plenty of cells. Subcultured cells were inoculated into denuded rat tracheal grafts at density of - 10^4 cells/graft, and the grafts were implanted into nude mice. Three weeks later, human neutrophil elastase ( - 3OOmu/graft) was injected into the graft lumen in order to induce mucus cell hyperplasia. The grafts were examined 4 weeks after the injection. The newly established epithelium in denuded tracheas was rather atrophic in the first series of the experiments, and later showed well-developed mucociliary epithelium ; the results were improved by changing the in vitro culture condition. Elastase stimuli have evoked no morphological change in the graft epithelium so far. Further investigation will be necessary for establishment of this culture model.
Immunonistochemical study of SLPI in various non-neoplastic pulmonary diseases indicated that SLPI-positive cells were seen in serous cells of tracheobronchial glands, surface mucous cells. Namely, incidence of SLPI-positive mucous cells was closely related to mucous cell hyperplasia. Interestingly, SLPI-positive bronchiolar Clara cells were rarely observed in a few case of acute, purulent bronchopneumonia. SLPI is well known to have anti-elastase activity, and elastase is one of representative substance to induce mucous cell hyperplasia and mucus hypersecretion. Therefore, unusual occurrence of SLPI-positive cells may act as inhibitors against increased-elastase derived from infiltrating neutrophils.
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