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.

过敏性疾病包括白细胞浸润和血管通透性增加，其中多种蛋白酶系统被认为参与其中。本研究的目的是纯化各种内源性蛋白酶抑制剂，研究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。 1．皮肤中的蛋白酶抑制剂。分别在正常皮肤部位和结核菌素皮肤部位发现激肽释放酶抑制剂和<alpha_2>-大白蛋白(<alpha_2>-MA)。发现这两种抑制剂与血浆中各自的抑制剂相同。2．血浆蛋白酶抑制剂。血浆 <alpha_2> -MA 是高度纯化的，并且被发现可以抑制由激活的哈格曼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。 <α_2>-MA与抗原一起注射到豚鼠皮肤中时，不会抑制牛<γ>-球蛋白和结核菌素迟发型超敏反应（DHR）中的IVP。然而，在通过血管内注射抗<alpha_2>-MA兔抗体诱导的<alpha_2>-MA耗尽的豚鼠中，0小时时的IVP被强烈抑制。这表明<alpha_2>-MA参与了DHR中IVP的调节，需要进一步研究。高纯度血浆激肽释放酶抑制剂可抑制注射激肽释放酶诱导的 IVP，但在 DHR 中未发现抑制活性。各种条件下的体内实验还需进一步研究。 3．胰蛋白酶样蛋白酶的血浆抑制剂，参与巨噬细胞趋化因子的产生。激肽释放酶抑制剂在体外抑制了蛋白酶活性，然而，检测巨噬细胞浸润调节活性的体内实验仍有待完成。