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首页> 外文期刊>Acta Pharmacologica Sinica >Inhibition of tryptase and chymase induced nucleated cell infiltration by proteinase inhibitors
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Inhibition of tryptase and chymase induced nucleated cell infiltration by proteinase inhibitors

机译：蛋白酶抑制剂抑制类胰蛋白酶和糜酶诱导的有核细胞浸润

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AIM: To investigate the ability of proteinase inhibitors to modulate nucleated cell infiltration into the peritoneum of mice induced by tryptase and chymase. METHODS: Human lung tryptase and skin chymase were purified by a similar procedure involving high salt extraction, heparin agarose affinity chromatography followed by S-200 Sephacryl gel filtration chromatography. The actions of proteinase inhibitors on tryptase and chymase induced nucleated cell accumulation were examined with a mouse peritoneum model. RESULTS: A selective chymase inhibitor Z-Ile-Glu-Pro-Phe-CO_2Me (ZIGPPF) was able to inhibit approximately 90 % neutrophil, 73 % eosinophil, 87 % lymphocyte and 60 % macrophage accumulation induced by chymase at 16 h following injection. Soy bean trypsin inhibitor (SBTI), chymostatin, and α_1-antitrypsin showed slightly less potency than ZIGPPF in inhibition of the actions of chymase. While all tryptase inhibitors tested were able to inhibit neutrophil, eosinophil, and macrophage accumulation provoked by tryptase at 16 h following injection, only leupeptin, APC366, and aprotinin were capable of inhibiting tryptase induced lymphocyte accumulation. The inhibitiors of tryptase tested were also able to inhibit tryptase induced neutrophil and eosinophil accumulation at 6 h following injection. When being injected alone, all inhibitors of chymase and tryptase at the concentrations tested by themselves had no significant effect on the accumulation of nucleated cells in the peritoneum of mice at both 6 h and 16 h. CONCLUSION: Proteinase inhibitors significantly inhibited tryptase and chymase-induced nucleated cell accumulation in vivo, and therefore they are likely to be developed as a novel class of anti-inflammatory drugs.
机译：目的：探讨蛋白酶抑制剂调节类胰蛋白酶和糜酶诱导的小鼠有核细胞向腹膜浸润的能力。方法：采用相似的方法纯化人肺类胰蛋白酶和皮肤糜酶，包括高盐提取，肝素琼脂糖亲和层析，S-200 Sephacryl凝胶过滤层析。用小鼠腹膜模型检查蛋白酶抑制剂对类胰蛋白酶和糜酶诱导的有核细胞积累的作用。结果：选择性糜蛋白酶抑制剂Z-Ile-Glu-Pro-Phe-CO_2Me（ZIGPPF）能够在注射后16 h抑制糜酶诱导的约90％的中性粒细胞，73％的嗜酸性粒细胞，87％的淋巴细胞和60％的巨噬细胞蓄积。大豆胰蛋白酶抑制剂（SBTI），乳糜蛋白酶和α_1-抗胰蛋白酶在抑制糜酶作用方面的效力比ZIGPPF略低。尽管测试的所有类胰蛋白酶抑制剂均能够抑制注射后16小时由类胰蛋白酶引起的嗜中性粒细胞，嗜酸性粒细胞和巨噬细胞蓄积，但只有亮肽素，APC366和抑肽酶才能够抑制类胰蛋白酶诱导的淋巴细胞蓄积。被测试的类胰蛋白酶的抑制剂还能够在注射后6小时抑制类胰蛋白酶诱导的嗜中性粒细胞和嗜酸性粒细胞的积累。当单独注射时，所有糜蛋白酶和类胰蛋白酶抑制剂以其自身测试的浓度在6 h和16 h对小鼠腹膜中有核细胞的积累均无明显影响。结论：蛋白酶抑制剂在体内显着抑制类胰蛋白酶和胰凝乳蛋白酶诱导的有核细胞积累，因此它们有可能被开发为一类新型的抗炎药。

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