1998 Fiscal Year Final Research Report Summary
THE INFLAMMATORY ACTIVITIES OF MAST CELL PROTEINASES TRYPTASE AND CHYMASE.
| Project/Area Number |
09670230
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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 |
Experimental pathology
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| Research Institution | KUMAMOTO UNIVERSITY |
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Principal Investigator |
IMAMURA Takahisa KUMAMOTO UNIVERSITY SCHOOL OF MEDICINE、ASSOCIATE PROFESSOR., 医学研究科, 助教授 (20176499)
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| Project Period (FY) |
1997 – 1998
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| Keywords | mast cell / tryptase / vascular permeability enhancement / allergy / chymase / elastase / bradykinin / B_2-receptor antagonist |
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| Research Abstract |
In order to study the pathophysiology of allergic reactions, mast cell proteases tryptase and chymase were investigated the inflammatory activities. Mast cell tryptase produced vascular permeability enhancement (VPE) activity from human plasma and kininogens. Tryptase releases bradykinin through prekallikrein activation and directly from kininogens. The tryptase VPE activity generation was augmented to 2-3 fold by mast cell chymase released together with tryptase. Neutrophil elastase also augmented the tryptase VPE activity production. Notably, neutrophil elastase by itself generated VPE activity from kininogens, indicating a new kinin liberation by elastase. To determine whether kinin generation is involved in VPE induced by allergic reactions, the effect of bradykinin B_2-receptor antagonist FR173657 was investigated using guinea pig allergy models. VTE induced by type I or type III allergic reactions was inhibited by the antagonist by 34% and 30%, respectively, suggesting a significant contribution of bradykinin to allergic reaction-induced VPE.
These results indicate that mast cell tryptase is a potent chemical mediator of allergic inflammation and its inflammatory activity is augmented by mast cell chymase and neutrophil elastase. The development of these proteinase-specific inhibitors, therefore, would be linked to therapeutic contribute to allergic diseases.
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Research Products
(8 results)
