Treatment of Inflammmation by Purified Human Proteinase Inhibitor.

特发性肾病综合征（INS）复发患者血浆对热溶素（一种细菌蛋白酶抑制剂）的抑制活性明显高于缓解期、偶发蛋白尿和/或血尿和对照受试者。血浆Sephadex G-200凝胶层析显示热溶素抑制活性限制在大分子组分中，sepphacryl S-300层析纯化人血浆中α 2-巨球蛋白（alpha2-MU），证实热溶素抑制活性与α 2- mu一致。这些结果表明，肾病血浆α 2- mu抑制热溶素活性的增加有助于通过灭活这些生物体合成的蛋白酶来防御可能的入侵病原体。采用fitc标记的抗人alpha2-MU抗体（山羊）检测alpha2-MU在肾组织中的沉积。1例4岁男童，表现为类固醇性难治性肾病综合征，在光镜下发现肾小球弥漫性α 2- mu沉积，肾小球系膜弥漫性增生，部分透明化。开始服用甲磺酸卡莫司他，一种市售的合成蛋白酶抑制剂，他对治疗反应良好。小鼠腹腔注射α 2- mu后，系膜内可见α 2- mu颗粒沉积。肾小球中α 2- mu的沉积可能直接提示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alpha2-MU时，蛋白酶抑制活性显著降低，这意味着alpha2MU的蛋白酶抑制能力降低。α 2- mu蛋白酶抑制能力的下降与血浆对正常淋巴细胞母细胞发生的抑制活性显著相关。与游离的alpha2-MU相比，纯化的alpha2-MU与胰凝乳酶络合，能强烈抑制由豆豆蛋白A诱导的正常淋巴细胞的形成。纯化的α 2- mu可轻微改善肾病血浆诱导的血管通透性。少

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