1998 Fiscal Year Final Research Report Summary
Study of the mechanisms for chronic allergic disease and application to drug research
| Project/Area Number |
09672267
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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 |
Biological pharmacy
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| Research Institution | TOKUSHIMA BUNRI UNIVERSITY |
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Principal Investigator |
AKAGI Masaaki Dep.of Pharmacol., Fac.of Pharm.Sci., TOKUSHIMA BUNRI UNIVERSITY Professor, 薬学部, 教授 (90093658)
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| Project Period (FY) |
1997 – 1998
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| Keywords | Allergic Inflammation / Mast cells / Histamine / Chemokines / Eosinophils |
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| Research Abstract |
Female Hartley guinea pigs were used. Guinea pigs were sensitized using egg albumin, and 14 days after, antigen solution was applied to the nasal mucosa. Immediate type of allergic reaction, the increase of vascular permeability, the sneezing and the scratching, was elicited. The nasal septum was collected, sectioned and stained using Luna staining 6, 12, 24, 48, 72hrs after application. l2hrs after, the accumulation of eosinophils significantly increased in nasal mucosa. The increase was significantly inhibited by anti-PAF and anti-LT drugs, and partially inhibited by anti-histamines, And the increase of expression of MIP-1 alpha mRNA was induced in nasal mucosa. Because we have observed the increase of expression of MIP-1 alpha mRNA in rat peritoneal mast cells induced by antigen-antibody reaction, the results suggest the contribution of mast cells to the expression of MIP-1 alpha mRNA in nasal mucosa. When histamine was applied to the nasal mucosa of non-sensitized guinea pigs, eosinophils were accumulated through H1 receptors, as well as that induced by antigen-antibody reaction. Hydrogen peroxide also increased the expression of MIP-1 alpha mRNA in mast cells and the increase was inhibited by catalase. And I confirmed the binding sites of superoxide-associated transcription factors in the promotor region of MIP-1 alpha. These results suggest that in the chronic allergic disease, histamine and superoxide released from mast cells induced by antigen-antibody reaction through IgE may enhance the production of chemokine such as MIP-1 alpha in the peripheral cells and the accumulated eosinophils may contribute to the prolongation and enlargement of the allergic disease.
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