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

变应性疾病主要表现为白细胞浸润和血管通透性增高，可能与多种蛋白酶系统有关。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变态反应性疾病的体内调节，最终开发人类变态反应性疾病的治疗手段。皮肤中的蛋白酶抑制剂。在正常皮肤和结核菌素皮肤部位分别发现Kallikrein抑制剂和<alpha_2> -MA。这两种抑制剂被发现与血浆中各自的抑制剂相同。血浆蛋白酶抑制剂。血浆< α _2> -MA具有抑制Hageman因子激活诱导的豚鼠皮肤血管通透性（IVP）升高的作用。< α _2> -MA抗原注射豚鼠皮肤后，对牛< γ > -球蛋白和结核菌素迟发性超敏反应（DHR）的IVP无抑制作用。然而，在<alpha_2> - ma缺失的豚鼠血管内注射抗<alpha_2> - ma兔抗体，0小时的IVP被强烈抑制。提示<alpha_2> -MA参与了DHR中IVP的调控，有待进一步研究。高纯度血浆钾化因子抑制剂对注射钾化因子诱导的IVP有抑制作用，但对DHR无抑制作用。需要在不同条件下的体内实验中进一步研究。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。Kallikrein抑制剂在体外抑制蛋白酶活性，但在体内实验中检测其对巨噬细胞浸润的调节活性还有待进一步研究。

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.