Development of The Endogenous Protease Inhibitor for the Treatment of Allergic Diseases
| Project/Area Number |
58870031
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| Research Category |
Grant-in-Aid for Developmental Scientific Research
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| Allocation Type | Single-year Grants |
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| Research Field |
Experimental pathology
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| Research Institution | Kumamoto University |
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Principal Investigator |
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| Project Period (FY) |
1983 – 1985
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| Project Status |
Completed (Fiscal Year 1985)
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| Budget Amount *help |
¥3,900,000 (Direct Cost: ¥3,900,000)
Fiscal Year 1985: ¥600,000 (Direct Cost: ¥600,000)
Fiscal Year 1984: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 1983: ¥2,300,000 (Direct Cost: ¥2,300,000)
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| Keywords | Allergy / Inflammation / Treatment / Endogenous inhibitor / Protease inhobitor / Macroalbumin / Kallikrein inhibitor / Activated Hageman |
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| Research Abstract |
Allergic diseases consist of leukocyte infiltration and increased vascular permeability, in which various protease system are suggested to be involved. The purpose of this study is to purify the various endogenous protease inhibitors, to study how the inhibitors are involved in the in vivo regulation of allergic diseases, and finally to develop the curative means of human allergic diseases.
1. Protease inhibitors in the skin. Kallikrein inhibitors and <alpha_2> -macroalbumin ( <alpha_2> -MA) were found in the normal and tuberculin skin sites, respectively. These two inhibitors were found to be identical to the respective inhibitors in plasma.
2. Plasma protease inhibitors. Plasma <alpha_2> -MA was highly purified and was found to inhibit increased vascular permeability(IVP) induced by activated Hageman Factor, which was found in the guinea pig skin and induced IVP. <alpha_2> -MA, when injected into guinea pig skin with antigen, did not suppress IVP in delayed hypersensitivity reaction(DHR) to bovine <gamma> -globulin and tuberculin. However, in the <alpha_2> -MA-depleted guinea pig, induced by intravascular injection of anti- <alpha_2> -MA rabbit antibody, IVP at 0 hour was strongly suppressed. This suggest the involvement of <alpha_2> -MA in the regulation of IVP in DHR, and needs further study. Highly purified plasma kallikrein inhibitor suppressed IVP induced by kallikrein injection, but found no suppressive activity in DHR. It needs further study under various conditions in in vivo experiments.
3. Plasma inhibitor for trypsin-like protease which invovlved in the generation of chemotactic factor for macrophages. Kallikrein inhibitor suppressed the protease activity in vitro, however, in vivoexperiment to detect the regulatory activity in the macrophage infiltration remains to be done.
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Report
(1 results)
Research Products
(6 results)
