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Treatment of Inflammmation by Purified Human Proteinase Inhibitor.

用纯化的人蛋白酶抑制剂治疗炎症。

基本信息

批准号：
63570430
负责人：
ASAMI Tadashi
金额：
$ 1.28万
依托单位：
Niigata University
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (C)
财政年份：
1988
资助国家：
日本
起止时间：
1988 至 1990
项目状态：
已结题

项目摘要

Inhibitory activity of plasma on thermolysin, a bacterial proteinase inhibitor, was significantly higher in patients with Idiopathic Nephrotic Syndrome (INS) at relapse than in those in remission, chance proteinuria and/or hematuria and control subjecets. Sephadex G-200 gel-chromatography of plasma revealed the thermolysin inhibitory activity confined in the large molecular fractions, and Sephacryl S-300 chromatography, performed to purify alpha2-macroglobulin ( alpha2-MU) from human plasma, demonstrated the coincidence of the thermolysin inhibitory acitivity with alpha2-MU. These results suggest that the increased thermolysin ihnibitory activity of nephrotic plasma alpha2-MU contributes as a defense against possible invasion pathogens by inactivating proteinases elaborated by these organisms.alpha2-MU was examined for deposition in kidney tissue, using FITC-labelled anti-human alpha2-MU antibody (goat). A four-year-old male, exhibiting steroid refractory nephrotic syndrome, was found … More to have diffuse deposition of alpha2-MU in the glomeruli which showed diffuse mesangial proliferation and partial hyalinizati on by light microscopy. Administration of Camostat mesillate, a commercially available synthetic proteinase inhibitor, was started and he responded well to the therapy. Granular deposition of alpha2-MU was demonstrated in the mesangium of mice after the intraperitoneal injection of alpha2-MU. The deposition of alpha2-MU in the glomeruli may directly suggest the participation of proteinase (s) and proteinase inhibitor (s) in the inflammatory processes.In INS, proteinase inhibitory activity was significantly decreased when calculated per one mole of alpha2-MU, implicating a reduced proteinase inhibiting capacity of alpha2MU. The decreased proteinase inhibiting capacity of alpha2-MU was significantly associated with the inhibitory activity of plas ma on normal lymphocyte blastogenesis. Purified alpha2-MU complexed with chymotrypsin, intensively inhibited normal lymphocyte blastogenesis, induced by Concanavalin A, as compared to free alpha2-MU. Vascular permeability induced by nephrotic plasma was slightly ameliorated by the administration of purified alpha2-MU. Less

特发性肾病综合征（INS）复发患者血浆对嗜热菌蛋白酶（一种细菌蛋白酶抑制剂）的抑制活性显著高于缓解期、偶发性蛋白尿和/或血尿患者及对照组。SephadexG-200凝胶层析显示嗜热菌蛋白酶抑制活性局限于大分子组分，SephacrylS-300层析从人血浆中纯化α 2-巨球蛋白（α 2-MU），证明嗜热菌蛋白酶抑制活性与α 2-MU一致。这些结果表明，增加嗜热菌蛋白酶抑制活性的肾病血浆α 2-MU有助于作为一种防御可能的入侵病原体通过灭活蛋白酶阐述了这些有机体。α 2-MU的沉积在肾组织中进行了检查，使用FITC标记的抗人α 2-MU抗体（山羊）。一个四岁的男性，表现为类固醇难治性肾病综合征，被发现 ...更多信息光镜下可见肾小球内α 2-MU弥漫性沉积，表现为弥漫性系膜增生和部分玻璃样变。开始给予卡莫司他甲磺酸盐（一种市售合成蛋白酶抑制剂），患者对治疗反应良好。在腹膜内注射α 2-MU后，在小鼠的系膜中证实了α 2-MU的颗粒沉积。α 2-MU在肾小球中的沉积可能直接表明蛋白酶和蛋白酶抑制剂参与炎症过程，在INS中，当计算每摩尔α 2-MU时，蛋白酶抑制活性显著降低，暗示α 2-MU的蛋白酶抑制能力降低。α_2-MU蛋白酶抑制能力的降低与血浆对正常淋巴细胞母细胞生成的抑制活性显著相关。与游离α 2-MU相比，纯化α 2-MU与胰凝乳蛋白酶复合，强烈抑制伴刀豆球蛋白A诱导的正常淋巴细胞胚细胞生成。通过施用纯化的α 2-MU，肾病血浆诱导的血管通透性略有改善。少