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Development of The Endogenous Protease Inhibitor for the Treatment of Allergic Diseases

治疗过敏性疾病的内源性蛋白酶抑制剂的研制

基本信息

批准号：
58870031
负责人：
KAMBARA Takeshi
金额：
$ 2.5万
依托单位：
Kumamoto University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Developmental Scientific Research
财政年份：
1983
资助国家：
日本
起止时间：
1983 至 1985
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-58870031/
关键词：
Allergy Inflammation Treatment Endogenous inhibitor Protease inhobitor Macroalbumin Kallikrein inhibitor Activated Hageman

项目摘要

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.

变应性疾病是由白细胞浸润和血管通透性增加引起的，各种蛋白酶系统参与了变应性疾病的发生。本研究的目的是纯化各种内源性蛋白酶抑制剂，研究这些抑制剂如何参与过敏性疾病的体内调节，最终开发人类过敏性疾病的治疗手段.皮肤中的蛋白酶抑制剂。激肽释放酶抑制剂和-巨清蛋白（-MA）被发现在正常和结核菌素皮肤网站，分别。<alpha_2><alpha_2>发现这两种抑制剂与血浆中的相应抑制剂相同。血浆蛋白酶抑制剂。血浆-MA是高度纯化的，并被发现抑制由激活的Hageman因子诱导的血管通透性增加（IVP），该因子存在于豚鼠皮肤中并诱导IVP。<alpha_2><alpha_2>- MA与抗原一起注入豚鼠皮肤，对牛球蛋白和结核菌素的迟发型超敏反应（DHR）无抑制作用。<gamma>然而，在-MA耗尽豚鼠，诱导血管内注射抗-MA兔抗体，IVP在0小时强烈抑制。<alpha_2><alpha_2>这表明-MA参与了DHR时IVP的调节，需要进一步研究。<alpha_2>高纯度的血浆激肽释放酶抑制剂可抑制注射激肽释放酶诱导的IVP，但对DHR无抑制作用。在各种条件下的体内实验有待进一步研究.参与巨噬细胞趋化因子生成的胰蛋白酶样蛋白酶的血浆抑制剂。激肽释放酶抑制剂在体外抑制蛋白酶活性，但在体内实验中检测巨噬细胞浸润的调节活性仍有待于做。